Intermediate effects of the ileocaecal urinary reservoir (Charleston pouch 1) on serum vitamin B12 concentrations: can vitamin B12 deficiency be prevented?

Authors


N.K.Bissada, MD, Professor and Chief of Urologic Oncology, Vice Chairman, Department of Urology, MUSC, 96 Jonathan Lucas St., HE644, PO Box 250620, Charlston, SC 29425, USA. e-mail: Graterb@musc.edu

Abstract

OBJECTIVE

To assess the long-term effects of a form of ileocolic urinary reservoir (Charleston Pouch 1) on vitamin B12 serum levels, as vitamin B12 deficiency may be an important long-term risk after urinary diversion by this method.

PATIENTS AND METHODS

The study included 60 patients (mean age 52 years, range 27–77; 33 men and 27 women) who had a follow-up of ≥ 36 months (36–132 months) after the construction of an ileocaecal urinary reservoir. Vitamin B12 serum levels were determined at the time of diversion and again when the patients were evaluated every 6 months.

RESULTS

Fifty-eight patients had a normal serum vitamin B12 concentration before surgery (two patients were excluded from the study because they had low levels); the mean level was 464 pg/mL (normal range 247–1000). At 6 and 12 months, the mean vitamin B12 levels were 367.5 and 468.5 pg/mL; at 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 11 years, the mean levels were 305, 495.5, 436.5, 379.5, 423.5, 393, 529.5, 631, 333.5 and 340 pg/mL, respectively.

CONCLUSION

Ileocaecal urinary reservoirs have no adverse effects on serum vitamin B12 levels for up to 10 years after surgery. Patients with vitamin B12 deficiency must be identified and given adequate parenteral doses for life. Because body stores of vitamin B12 may not be depleted for many years, problems with B12 may be masked for a long time. We recommend that vitamin B12 levels be obtained annually, that a modest supplement twice yearly (by injection) may be beneficial and that serum vitamin B12 must be sampled before giving vitamin B12 injections, to avoid false results.

INTRODUCTION

Many nutritional problems may occur as a result of the loss of part of the intestinal absorptive surface when substantial portions of the gut are removed to construct urinary intestinal diversions. In a patient with significant loss of ileum, vitamin B12 malabsorption has been reported to result in pernicious anaemia and neurological abnormalities [1]. Vitamin B12 deficiency occurred in 10 of 41 patients who received radiotherapy before radical cystectomy and ileal ureterostomy [2]. Loss of the ileocaecal valve can have adverse effects, as reflux of a large concentration of bacteria into the ileum results in overgrowth of small intestinal bacteria. This can cause bacterial metabolism of vitamin B12, leading to its deficiency. These reports cause concern that vitamin B12 deficiency might be an important long-term risk after urinary diversion using an ileocolic segment. Herein, we assessed the intermediate effects of using an ileocolic segment as a urinary reservoir on vitamin B12 serum levels.

PATIENTS AND METHODS

The study included 60 patients (33 men and 27 women, mean age 52 years, range 27–77) with a form of ileocolic urinary reservoir (Charleston pouch 1), and who had a follow-up of ≥ 36 months (36–132 months). Indications for diversion were after cystectomy for invasive bladder cancer in 49, and other in 11. Six patients had had a previous ileal conduit before conversion to a continent urinary diversion. Vitamin B12 serum levels were measured at the time of diversion and again when the patients were evaluated every 6 months. Because of concern about the consequences of developing vitamin B12 deficiency, patients routinely received a modest dose of vitamin B12 by injection (100 µg), starting 6 months after surgery and twice per year.

RESULTS

Fifty-eight patients had normal serum vitamin B12 levels before surgery; one women was diagnosed with pernicious anaemia (with neurological and haematological manifestations) and was receiving monthly vitamin B12 injections, and another had a low serum vitamin B12 level with no clinical manifestations. These two patients were maintained on monthly injections and excluded from the analyses. The mean (range) initial serum vitamin B12 level in the 58 patients was 464 (247–681) pg/mL (normal range 247–1000). Because of the initial observation that high levels of vitamin B12 were measured immediately after intramuscular injections with vitamin B12, such samples were excluded and subsequent measurements obtained before injection. Excluding the two patients with known vitamin B12 deficiency, at 6 and 12 months the mean (range) serum vitamin B12 was 367.5 (256–479) and 468.5 (238–699) pg/mL; at 18 months it was 305 (181–429) pg/mL. Only one patient (white man) had a low vitamin B12 level at 18 months, was given a standard dose of vitamin B12 (100 µg) and had a normal level on subsequent follow-up. At 2 years, the vitamin B12 level was 495.5 (397–594) pg/mL, and subsequent mean values were: 436.5, 379.5, 423.5, 393, 529.5, 631, 333.5 and 340 pg/mL at 3, 4, 5, 6, 7, 8, 10 and 11 years, respectively.

DISCUSSION

The prevalence of vitamin B12 deficiency increases as people age [3,4]; as documented by both low serum vitamin B12 levels and more recently by elevated levels of two vitamin B12-dependent metabolites, methylmalonic acid and total homocysteine, in the serum of older subjects [5–7]. Some of these subjects have true pernicious anaemia (1.9% of those aged ≥ 65 years), but most are thought to have malabsorption of protein-bound vitamin B12 [8]. The natural history of protein-bound B12 malabsorption is unknown, especially because these individuals may absorb crystalline B12, which is found in small amounts in vitamin supplements and in food [3]. Vitamin B12 deficiency is defined as a serum B12 level of < 190 pg/mL (range 190–300) [9]. The prevalence of metabolically confirmed B12 deficiency was 14.5% in older outpatients in the early 1990s; most clinically deficient patients have concentrations of methylmalonic acid of> 500 nmol/L [7].

One of the remarkable changes with ageing is the frequent development of atrophic gastritis and the inability to secrete gastric acid. This process affects about a third of older adults in the USA and was only recently recognized to be caused by infection with Helicobacter pylori in most cases. The lack of gastric acid in atrophic gastritis may lead to small intestinal bacterial overgrowth and influence the absorption of vitamin B12 [10]. None of the present 58 patients with normal initial B12 levels developed consistently low serum B12 levels throughout the study. Fujisawa et al.[11] reported that 16.6% of patients with an ileocolic neobladder developed lower serum vitamin B12 levels after 5–6 years. The reported risk of vitamin B12 deficiency is 30% and 33% at 3 and 5 years in patients with an orthotopic Kock ileal neobladder [12]. Steiner et al.[13] reported that 25% of patients with an ileocolic neobladder had low serum vitamin B12 levels, and they recommended that such patients must be identified and placed on lifelong parenteral vitamin B12. Narayan et al.[14] reported that all patients with an ileocaecal pouch had reduced vitamin B12 levels, but no megaloblastic anaemia. Terai et al.[15] reported that the mean serum B12 level in patients with the Kock pouch (506 pg/mL) and the Indiana pouch (536 pg/mL) were lower than in patients with an ileal conduit (727 pg/mL). The mean serum B12 levels were not significantly different between patients with and without preoperative irradiation. A third of patients with Kock pouches and two-thirds with Indiana pouches were B12 malabsorbers, although no patients had megaloblastic anaemia or neurological symptoms. The present patients showed no abnormally low serum vitamin B12 levels over 4–11 years of follow-up. Whether the modest dose of vitamin B12 influenced these results is speculative, but the present study shows that with modest supplements vitamin B12 deficiency is not clinically significant in the first decade after constructing an ileocaecal reservoir.

In conclusion, the Charleston pouch has no critical adverse effects on serum vitamin B12 levels over at least 10 years. Patients with initial vitamin B12 deficiency must be identified and given adequate doses of parenteral vitamin B12 for life. Because body stores of vitamin B12 may not be depleted for many years, problems with B12 may be masked for a long time. We recommend that vitamin B12 levels be measured annually, that a modest supplement of twice yearly vitamin B12 injections may be beneficial, and that serum vitamin B12 must be sampled before giving B12 injections, otherwise serum vitamin B12 levels are overestimated.

REFERENCES

COMMENT

When using bowel segments in urinary diversion, metabolic disturbances may occur after surgery [1–3], during two important periods. After catheter removal, a new balance must develop between the additional absorption and secretion of solutes from and into the urine exposed to bowel mucosa in the newly formed reservoir. These changes can cause severe problems in different body systems. For example, an imbalance of the acid-base status may lead to fatal complications if not detected in time. Treatment with sodium/potassium citrate or bicarbonate usually solves these problems.

In the long-term another system is more relevant. Removing absorptive surface from the gastrointestinal tract to create the urinary reservoir can lead to deficiencies in certain proteins, vitamins, acids, etc. Here, Yakout and Bissada report one of these intermediate or long-term problems, vitamin B12 deficiency. Two factors are essential for vitamin B12 absorption, an intrinsic factor and the absorptive surface of the ileum [2]. The intrinsic factor is produced by the parietal cells of the stomach, and complexes with vitamin B12, a member of the family of cobalamins; the complex is then absorbed in the distal small bowel. Because humans cannot produce vitamin B12, they are completely dependent on vitamin B12 uptake from dietary sources [4]. The total body store of vitamin B12, which is predominantly in the liver, is 2–5 mg. Even with no vitamin B12 uptake it takes 4–5 years before low vitamin B12 levels are detectable in patients, provided they have normal levels initially. Patients with vitamin B12 deficiency before surgery must be identified as they require lifelong supplementation, as noted by the authors.

This report raises an important issue about the follow-up after urinary diversion. Vitamin B12 deficiency may lead to severe haematological and neurological symptoms, which include megaloblastic anaemia, peripheral neuropathy, optical atrophy, dementia, and funicular myelosis (spinal cord degeneration) [2–6].

The risk of vitamin B12 deficiency depends on the length of ileum used [2]. In pathological conditions such as Crohn's disease, the critical length of ileum resected to induce vitamin B12 malabsorption is 50–60 cm [7–8]. Yakout and Bissada focus on the ileocaecal segment when reporting their results with the Charleston Pouch 1. They did not find that vitamin B12 levels consistently decreased when they supplemented with 100 µg every 6 months for the follow-up of up to 11 years. This is in contrast to other studies which showed decreased vitamin B12 levels in patients with an ileocaecal urinary diversion in 10–25% after an intermediate follow-up [9–11]. In our studies [3,4], mean vitamin B12 levels were normal during a follow-up of> 4 years in 137 patients after diversion with the Mainz Pouch I (constructed of 12 cm of ascending colon and 24–36 cm of terminal ileum, including the ileocaecal valve). Nevertheless, there was a significant decrease in extracellular vitamin B12 levels 2–4 years after surgery, suggesting that the loss of absorptive surface is responsible for the decrease in vitamin B12 levels. There were no clinical symptoms related to vitamin B12 deficiency in our studies. In the most recent study [12] of 94 patients with a Mainz Pouch I, no vitamin B12 supplements and a median (range) follow-up of 9 (5–16) years, there was no statistical difference in the vitamin B12 levels between patients with a follow-up of 5–10 years and those with> 10 years of follow-up. This suggests that a steady state is reached after 4–5 years. However, vitamin B12 levels were low-normal or abnormally low in 32% of the patients, for whom we subsequently recommended vitamin B12 supplements. None of our patients had clinical symptoms related to vitamin B12 deficiency in this study.

Other variables that can be useful to detect vitamin B12 deficiency are methylmalonic acid and homocysteine, as noted by the authors. The reliability of these tests is questionable, as Sagalowski and Frenkel [11] detected high levels of both in 33% and 47% of patients, respectively, with an ileal conduit, after a mean follow-up of only 1.6 years. This would mean that about half of the patients with an ileal conduit already show deficiency after 1.6 years. Another new marker to predict vitamin B12 deficiency at an earlier stage, holotranscobalamin, was recently reported [5], which represents the fraction of cobalamins bound to the transport protein transcobalamin. Plasma levels of holotranscobalamin correlate better with malabsorption than plasma cobalamin levels. This variable needs to be validated in patients with urinary diversion.

In the present study all patients had a parenteral supplement every 6 months, thus preventing vitamin B12 deficiency. From our data we prefer to determine vitamin B12 levels and then give supplements at low levels. This approach might be more expensive, but avoids supplementing two-thirds of our patients who do not need it.

Dr. Jesco Pfitzenmaier Department of Urology, Johannes Gutenberg-University Mainz, Mainz, Germany

e-mail: jpfitx.gmx.net

REFERENCES

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