Clinical assessment to determine the risk of bowel cancer using Symptoms, Age, Mass and Iron deficiency anaemia (SAMI).

BACKGROUND: The aim of this study was to identify characteristics with independent predictive value for bowel cancer for use in the clinical assessment of patients attending colorectal outpatient clinics. METHODS: This was a 22-year (1986-2007) retrospective cohort analysis of data collected prospectively from patients who attended colorectal surgical outpatient clinics in Portsmouth. The data set was split randomly into two groups of patients to generate and validate a predictive model. Multivariable logistic regression was used to create and validate a system to predict outcome. Receiver operating characteristic (ROC) curves and Hosmer-Lemeshow test were used to evaluate the model's predictive capability. The likelihood of bowel cancer was expressed as the odds ratio (OR). RESULTS: Data from 29 005 patients were analysed. Discrimination of the model for bowel cancer was high in the development (C-statistic 0·87, 95 per cent c.i. 0·85 to 0·88) and validation (C-statistic 0·86, 0·84 to 0·87) groups. The most important co-variables in the final model were: age (OR 3·17-27·10), rectal (OR 31·48) or abdominal (OR 1·83-8·45) mass, iron deficiency anaemia (IDA) (OR 4·42-8·38), rectal bleeding and change in bowel habit in combination (OR 5·37), change in bowel habit without rectal bleeding, with or without abdominal pain (OR 2·12-2·52), and rectal bleeding with no perianal symptoms and without change in bowel habit (OR 2·91). Some 91·5 per cent of bowel cancers presented with these characteristics, 40·4 per cent with a mass and/or IDA. In patients with at least one of these characteristics the overall risk of having cancer was 10·0 (range 6·5-50·4) per cent, compared with 1·1 (0·3-2·3) per cent in patients without them. CONCLUSION: A clinical assessment that systematically identifies or excludes four symptom-age combinations, a mass and IDA (SAMI) stratifies patients as having a low and higher risk of having bowel cancer. This could improve patient selection for referral and investigation.

Earlier diagnosis and treatment of symptomatic bowel cancer: can it be achieved and how much will it improve survival?

AIM: To determine current delays in diagnosis and treatment of bowel cancer, when and why they occur, and what effect they have on survival. METHOD: A detailed review of the literature based on the development of the GP referral guidelines in 2000. RESULTS: There is no evidence of a reduction in the delay to diagnosis and treatment of bowel cancer over the last 60 years. There is no strong theoretical basis for a benefit from earlier diagnosis of symptomatic bowel cancer and this is consistent with observational studies. CONCLUSION: Campaigns to earlier diagnose bowel cancer will not be successful unless new strategies are developed. There is substantial evidence that earlier diagnosis of symptomatic bowel cancer will not improve survival in the majority of patients. However as excessive delays still occur in some patients it is reasonable to continue to aim to diagnose and treat all bowel cancer within 6 months of the onset of symptoms with an overall median of 3-4 months.

Changes in rat renal cortex, isolated plasma membranes and urinary enzymes following the injection of mercuric chloride.

Some of the biochemical changes in rat kidney following the administration of mercuric chloride have been determined. Mercuric chloride had an immediate effect on the renal brush border resulting in rapid loss of the microvilli. Plasma membranes were isolated and characterised at various stages in the necrotic process, mircovilli were absent from these preparations and the activities of marker enzymes for the brush border were significantly decreased. In contrast the basal plasma membranes were unaffected by the nephrotoxin during the early stages and no change occurred in the activity of (Na+ + K+)-ATPase, a marker enzyme for the basal membranes. The change in the pattern of urinary enzyme excertion closely paralleled the ultrastructural changes in the tubular cells. The sequence of subcellular change following the administration of mercuric chloride is discussed in relation to the known mechanism of action of this agent.

A note on the practical aspects of the assay of N-acetyl-beta-glucosaminidase in human urine.

1. Some practical aspects of the assay of urinary N-acetyl-beta-glucosaminidase activity were studied in patients with renal disease. 2. Centrifugation and dialysis of urine were not necessary prior to assay. 3. When enzyme activity was related to urinary creatinine random urine samples could be used. 4. Since preservatives used to prevent bacterial growth may inhibit enzyme activities, samples should be assayed immediately after collection or stored at 4 degrees C or 20 degrees C. 5. Mild visible haemoglobinuria, eg. derived from lysed red blood cells did not interfere with the enzyme assay.

Urinary enzyme excretion during renal papillary necrosis induced in rats with ethyleneimine.

N-Acetyl-beta-glucosaminidase, beta-galactosidase, beta-glucosidase, acid and alkaline phosphatase were monitored in urine kidney homogenates and serum of rats with papillary damage induced with ethyleneimine. Serum urea levels, total protein in the urine and urine volume were monitored throughout the study. Histological studies showed that the injection of ethyleneimine caused immediate papillary necrosis, followed later by secondary cortical involvement. Minor papillary necrosis induced by a low dose (0.5 mul/kg) of ethyleneimine was characterised by a rise in urinary N-acetyl-beta-glucosaminidase activity which was followed later by an increase in the activity of the other enzymes monitored. More severe papillary necrosis induced with a higher dose of ethyleneimine (5.0 mul/kg) resulted in an immediate rise in the activities of all the urinary enzymes which then decreased only to rise again when cortical involvement occurred. Serum urea was unaltered but urine volume and protein were increased coincidentally with the urinary enzyme activities. The value of the assay of urinary enzymes in distinguishing papillary from glomerular and tubular damage is assessed. The possible relevance of the ethyleneimine model to the etiology of papillary nephropathy is discussed.

Presence of serum and tissue forms of N-acetyl-beta-glucosaminidase in urine from patients with renal disease.

1. The A, B, I1 and I2 forms of N-acetyl-beta-glucosaminidase present in urine, serum, kidney, liver and cerebral spinal fluid were separated on DEAE-cellulose and their presence confirmed by cellogel electrophoresis. The relative activities of each enzyme were determined by integrating the area under the elution peaks. 2. Serum A-form was eluted at a lower molarity of chloride than liver A-form and this was designated the As-form to distinguish it from the A-form of N-acetyl-beta-glucosaminidase found in liver and kidney. 3. The P-form of N-acetyl-beta-glucosaminidase present in the serum of a group of pregnant women was not detectable in urine samples from the same women. 4. Urinary NAG activities were found to be abnormally high in patients with impaired renal function. 5. The activity of both N-acetyl-beta-glucosaminidases A and B increased in pathological urines. The higher the total N-acetyl-beta-glucosaminidase activity excreted the higher the % of activity of the B-form present. 6. In a number of patients with haematuria an A-form similar to the serum As-form was present in the urine.

Urinary N-acetyl- beta-D-glucosaminidase activities in patients with renal disease.

Urinary N-acetyl-beta-D-glucosaminidase (NAG) activities were assayed in every urine void throughout 24 hours in 17 normal people and in four patients with renal disease. The variation in NAG activity due to changing rates of urine flow was almost eliminated by factoring enzyme activity by the urinary creatinine concentration. Random samples of urine may thus be used for assay. The results of NAG assay in 36 patients with acute and chronic renal diseases showed that NAG was a sensitive indicator of renal damage. This simple test may be valuable in detecting or monitoring renal disease.

Early warning of rejection?

The urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), beta-galactosidase (GAL), beta-glucosidase (GLU), and alkaline phosphatase (AP) was studied in 83 patients with renal allografts. Thirty of these patients had stable graft function and their urinary enzyme levels provided a range of normal values. Urinary lactic dehydrogenase (LDH) was estimated in 29 normal subjects and in 11 patients with renal allografts. Serum values for the five enzymes were also obtained. Urinary NAG excretion was abnormally high in 16 out of 17 (94%) episodes of acute rejection. The other urinary enzymes were raised less frequently. In nine patients studied before the onset of rejection urinary NAG activity rose up to three weeks before changes in other tests of renal function. Serum enzyme levels were not found to be of value in the diagnosis of rejection.