Colorectal Microcarcinoids in Association with Long-Term Exposure to Urinary Content: A Case Report and Review of the Literature

Long-term exposure of colonic mucosa to urinary content and its association with increased risk of infection, mechanical and biochemical irritation, and malignancy have been described in the literature. Existing case reports and studies depict the low but distinct risk of malignancy in gastrointestinal segments which come in contact with urinary content as a result of surgical correction of urinary tract abnormalities. However, these reports are largely limited to colonic adenocarcinoma and urothelial cell carcinoma. Late urointestinal carcinoma in patients with ileal incorporation into the urinary tract has also been reported. To the best of our knowledge, however, there is only one case report documenting neuroendocrine (NE) cell hyperplasia in colonic mucosa after long-term cystoplasty. Our case is the first to describe microcarcinoids and diffuse NE hyperplasia occurring in a patient with congenital anorectal anomalies, resulting in long-term exposure of colonic mucosa to fecal stream and urinary content. This case, in conjunction with the reported cases in the literature, raises the distinct possibility of an association between exposure of colonic mucosa to urine and long-term development of malignancy, including NE neoplasms.

Vesical Urothelium and New Concepts

Vesical urothelium was long considered to simply be a protection barrier, which passively separates the urinary content from the underlying smooth muscle and the blood stream. Recent observations, though, have pointed out that vesical urothelium cells have clear active and sensory functions, in response to various physical and chemical stimuli. Among these characteristics are the expression of several neurotransmitters and receptors: Acetylcholine, Nitric Oxide, VIP, CGRP, NKA, SP and cholinergic, vanilloid, purinergic, and tachykinin receptors. Urothelium-produced neurotransmitters are likely supposed to act through a receptor stimulation of the afferent nerve fibers within the sub-urothelial spaces. Sub-urothelial myofibroblasts are considered to play a mediation role between urothelium-produced neurotransmitters and the underlying receptors. According to these observations, a pharmacologic modulation, directly affecting the urothelium, can be hypothesized.

Absorption of epidermal growth factor and insulin in rabbit renal proximal tubules

Epidermal growth factor (EGF), which stimulates the growth of a variety of tissues, was originally isolated from mouse submandibular glands. Human EGF (hEGF) has been isolated from the urine, and cDNA encoding for EGF has been isolated from the human kidney. Thus the kidney may represent an alternate source of EGF. Another potential explanation for the urinary content of EGF is a limited reabsorption of filtered EGF and/or a transtubular transport of EGF from the peritubular compartment to the lumen. Therefore, we exposed isolated and perfused rabbit proximal tubules to 125I-hEGF either in the perfusate or in the bath fluid. Luminal uptake of hEGF was compared with uptake of 125I-porcine insulin, which is known to be taken up with large efficiency. The results demonstrate that only 4% of the perfused 125I-hEGF load was taken up per millimeter of tubule length compared with 73% for insulin. Furthermore, hEGF is subject to a small transtubular transport from bath to lumen. Renal clearance of endogenous rabbit EGF was also measured and was comparable with that of creatinine. Thus in conclusion this study strongly suggests that filtered EGF to a large extent remains in the ultrafiltrate, unlike insulin, which is removed within the first few millimeters of proximal tubule. In addition filtered EGF in preurine is probably supplied by EGF transported intact across the proximal tubular epithelium.

A SIMPLE COMPETITIVE PROTEIN-BINDING ASSAY FOR ADENOSINE-3′,5′-MONOPHOSPHATE IN PLASMA AND URINE

ABSTRACT A modified competitive protein-binding assay for the measurement of adenosine-3′,5′-monophosphate is desribed. The procedure allows measurement of adenosine-3′,5′-monophosphate in unextracted plasma samples. The mean plasma values in 25 normal, fasting and ambulatory subjects were 22.7 ± 4.7 pmol/ml (mean ± sd) (range 13–31 pmol/ml. The mean urinary content was 3.2 ± 1.0 μmol per g creatinine (mean ± sd) (n=24).

Urinary Excretion of 17-Oxosteroids in Hereditary Coproporphyria

1. Urinary 17-oxosteroid conjugates were measured by gas-liquid chromatography in five patients with hereditary coproporphyria. 2. Three patients were in an acute attack and showed significantly increased excretion of sulphate or glucuronide conjugates of aetiocholanolone. There was increased excretion of several other related steroids but no consistent pattern was apparent. 3. In the two patients in remission, excretion of urinary 17-oxosteroids was not increased. 4. The ratio of total urinary aetiocholanolone to androsterone (5β:5α) was found to be significantly elevated for the three patients in an acute attack. Serial measurements were made in two of these patients and showed a highly significant linear correlation between this ratio and the urinary content of δ-aminolaevulic acid and porphobilinogen. 5. These observations suggest the involvement of the 17-oxosteroids, especially aetiocholanolone, in the pathogenesis of hereditary coproporphyria.

ROUTINE DETERMINATIONS OF 17-KETOSTEROIDS AND PORTER-SILBER CHROMOGENS COMPARED WITH THE CHROMATOGRAPHIC MEASUREMENT OF GROUPED AND INDIVIDUAL STEROIDS

ABSTRACT The accuracy of two routine methods for the determination of urinary steroids – 17-ketosteroids (17-KS) and Porter-Silber chromogens – has been investigated by chromatographic separation and quantitative determination of individual 17-KS and Porter-Silber reacting steroids in 141 urine samples. For this purpose urine was submitted to enzyme hydrolysis and subsequent solvolysis. The pertinent steroids were separated by column chromatography into three groups, 11-deoxy-17-KS, 11-oxy-17-KS and Porter-Silber reacting steroids. The final separation was accomplished by paper chromatography. As a mean, the urinary excretion of true 17-KS corresponded to about 40–50 per cent of the routine figures. Due to non specific chromogens, individual routine figures were completely unreliable and probably had no more significance than showing a difference between a high and a low urinary content of 17-KS A true figure, however, was never higher than that indicated by the routine method. The routine method for determination of Porter-Silber chromogens also overestimated the urinary content of steroids, the true excretion of Porter-Silber steroids being, on an average, about 25 % lower. Again, the significance of individual determinations was low. The determination of 17-KS and Porter-Silber steroids by column chromatography was found to be rather simple and reliable as only minor amounts of unspecific chromogens were included in the results. Moreover with this method, the 17-KS were separated into 11-deoxy-17-KS and 11-oxy-17-KS.