Intact Pouch Research Articles

Functional Outcome and Quality of Life after Ileal Pouch-Anal Anastomosis within a Defined Population in Sweden

Objective: The purpose of this population-based study was to present prospectively recorded functional data and health-related quality of life (HRQOL) questionnaire data to assess the long-term results of the first 100 consecutive ileal pouch-anal anastomosis (IPAA) performed chronologically by 3 surgeons in a single referral centre. Methods: During 1993–2008, 100 patients underwent IPAA. The 90 patients still alive with an intact pouch were included (response rate = 92%). Function was evaluated using St Mark’s incontinence score, and HRQOL with SF-36. Results: At 18 months after loop ileostomy closure, 63 patients (76%) had 4–6 day-time and 47 patients (57%) had no night-time bowel movements. A stapled IPAA resulted in better St Mark’s (p = 0.0064) and Wexner scores (p = 0.0019) than did a hand-sewn anastomosis. The younger the patients were at the onset of ulcerative colitis (UC) the better St Mark’s (p = 0.0037) and Wexner scores (p = 0.011) were. The patients scored significantly higher than did the general Swedish population adjusted by age-group and sex in 6 out of 7 SF-36 subscales. Conclusions: In the hands of experienced high-volume surgeons, IPAA is a safe procedure associated with good functional results that are stable over time. Stapled IPAA and younger age at onset of UC were correlated with better functional results. The HRQOL scores were high.

Long‐term functional outcome after restorative proctocolectomy in patients with ulcerative colitis

The aim of this study was to evaluate the long-term functional outcome of ileal pouch-anal anastomosis for ulcerative colitis and to compare symptoms over time. In all, 188 patients were operated with an ileal pouch-anal anastomosis. Short-term functional outcome has previously been evaluated with a symptom questionnaire. The same questionnaire was sent to the 162 patients who were alive and had an intact pouch. A symptom index was studied over time and in relation to early complications and pouchitis. The response rate of the questionnaire was 139/162 at a median of 12.5 (9.5-21) years postoperatively. Overall, the symptom index remained unchanged over time but both the frequency of night-time defaecation and episodes of night-time incontinence increased. Patients' global assessment was unchanged with approximately 80% stating an excellent or a good result. Frequency of pouchitis doubled in 10 years. Symptom index for patients with episodic pouchitis [median 40 (8-89), P = 0.018] and recurrent/chronic pouchitis [71 (8-136), P < 0.001] was higher than in patients without pouchitis [29 (0-105)]. Early complications did not affect the symptom index. The overall functional outcome of ileal pouch-anal surgery for ulcerative colitis is stable over time. Patients' satisfaction with outcome remains high. Pouchitis is a determinant of functional outcome.

Outcome after restorative proctocolectomy in children and adolescents

The results including function and quality of life (QOL) of restorative proctocolectomy (RPC) performed in children and adolescents with ulcerative colitis (UC), familial adenomatous polyposis (FAP) and idiopathic megarectum were determined. Twenty-one patients of a median age of 15 (10-17) years underwent RPC between 1995 and 2006. The indication, use of covering ileostomy, morbidity and mortality were recorded. A structured questionnaire was completed by telephone interview to assess long-term function. The Cleveland Clinic Scoring (CCS) System was used for the assessment of faecal incontinence and the modified McMaster proforma for QoL. There was no mortality. At a median follow-up of 65.5 (26-168) months, all patients had an intact pouch. One had a long-standing ileostomy. Median daytime and nocturnal stool frequencies were 4 (2-16) and 0 (0-3). The mean CCS was 1.47, with only one patient scoring more than 10. Eighteen of 20 patients were satisfied with the result; two patients had a worse QoL (McMaster score >8). One patient had a permanent stoma following pouch sepsis and one had symptoms of pouchitis. RPC can be performed in children and adolescents with good functional outcome and acceptable QoL.

Long‐term functional outcome and quality of life after restorative proctocolectomy with ileo‐anal anastomosis for colitis

The study aimed to evaluate long-term health-related quality of life (HRQOL) and functional outcome in patients who had undergone restorative proctocolectomy with ileo-anal anastomosis (IPAA) for ulcerative colitis and familial adenomatous polyposis. A total of 156 patients who underwent IPAA during the period 1984-2003 and who still had an intact pouch were included. The HRQOL score was compared with 4152 individuals from the general Norwegian population using the SF-36 questionnaire, and function was evaluated using the Wexner Continence Grading Scale. One hundred and ten (71%) patients answered the questionnaires, 60 (55%) of whom were men. All except five patients had ulcerative colitis. Median (range) age at interview was 47 (19-66) years, and time after surgery was 12 (2-22) years. The IPAA patients scored slightly, but significantly, lower in four of six SF-36 health domains than the control subjects, adjusted for age and gender. Multiple regression analysis showed frequency of nocturnal defaecation, faecal incontinence and urgency to be independent negative prognostic factors of quality of life. Frequency of defaecation was a median of 7 (3-12) bowel movements during the day and 2 (0-6) at night. The majority had some degree of faecal incontinence, median (range) Wexner score of 8 (0-17), and 40% reported urgency of defaecation necessitating alterations in lifestyle. Patients with IPAA reported slightly lower HRQOL rates than the general population and had an inferior functional outcome.

Permanently increased mucosal permeability in patients with backwash ileitis after ileoanal pouch for ulcerative colitis

Objective. Backwash ileitis (BI) has not been identified as a risk factor for pouchitis. The aim of this study was to investigate the barrier function of the ileoanal pouch depending on the presence of BI. The incidence of pouchitis in a population of ulcerative colitis patients with BI is also reported. Material and methods. Biopsies were taken from 80 patients with ulcerative colitis: a) terminal ileum prior to pouch creation (pre-IAP); b) 16 months after ileostomy closure (intact pouch); and c) during pouchitis. Patients were stratified into the BI group and the non-BI (ØBI) group. Barrier function was determined in Ussing-chambers as epithelial resistance by impedance analysis and as mannitol permeability from 3H-mannitol fluxes. Na+-glucose co-transport was measured as a change in short-circuit current (ISC) after addition of glucose. Relative risk of developing pouchitis was calculated by corrected χ2 test. Results. In 13/21 (BI/ØBI) pre-IAP patients, 23/37 (BI/ØBI) with an intact pouch, and 35/7 (BI/ØBI) with pouchitis, epithelial resistance in BI/ØBI was 13.5±1.6/14.3±0.9 Ω·cm2 for pre-IAP, 12.7±1.3/16.8±1.2 Ω·cm2 (p<0.05 BI versus ØBI) for the intact pouch, and 10.1±1.1/9.9±1.8 Ω·cm2 for pouchitis (p<0.05 BI versus ØBI with an intact pouch). No differences were found for electrogenic chloride secretion and active Na+-glucose co-transport between BI/ØBI in the three groups. In patients with BI, pouchitis was more common (35 versus 7 patients, odds ratio 33.0 (95% CI 8.3–143.9; p<0.0001)). Conclusions. Ulcerative colitis patients with BI show impaired barrier function in the further course of the ileoanal pouch. Thus, BI has a long-term impact on epithelial barrier function.

Increased bacterial permeation in long-lasting ileoanal pouches

Bacterial overgrowth appears to play an important role in the pathogenesis of ileoanal pouches. Therefore, the capability of bacterial permeation and its determinants is of great interest. The aim of this study was to examine bacterial permeation in the ileoanal pouch and to correlate the results with the degree of inflammation, the epithelial resistance, the mucosal transport function, and the age of the ileoanal pouches. Biopsies were taken from 54 patients before colectomy (n = 13; preileal pouch-anal anastomosis [IPAA]), and closure of ileostomy (n = 7; deviation), <1 year after closure of ileostomy (n = 8; intact pouch I), >1 year after closure of ileostomy (n = 16; intact pouch II), in the case of pouchitis (n = 11), and in 11 controls. Tissues were mounted in a miniaturized Ussing chamber. Escherichia coli was added to the mucosal side of the Ussing chamber, and the permeation was proven by serosal presence of E. coli. Epithelial and subepithelial resistance was determined by transmural impedance analysis. Active Na-glucose cotransport and active Cl secretion were measured. Specimens were analyzed by fluorescent in situ hybridization with oligonucleotide probes targeting the bacterial 16s ribosomal RNA. The bacteria in and on the tissue were enumerated. Bacterial permeation occurred in 2 of 13 pre-IPAA, 2 of 7 deviations, 0 of 8 intact pouch I, 9 of 16 intact pouch II, 5 of 11 pouchitis specimens, and 0 of 11 ileum controls. The frequency of bacterial permeation in the intact pouch II group is higher than in the intact pouch I group (P < 0.001). Epithelial resistance, mannitol fluxes, electrogenic chloride secretion, sodium-glucose cotransport of the bacterially permeated specimens versus nonpermeated of the intact pouch II group, and the pouchitis group and subepithelial resistance remained unchanged. Intramural bacteria could be detected by fluorescence in situ hybridization mainly in long-lasting pouches, but there was no correlation with bacterial permeation. The long-lasting ileoanal pouch is associated with increased bacterial permeability. This is not correlated with a disturbed function of the pouch mucosa but could be a precursor of pouchitis.

Role of the Alternate Pathway of Dihydrotestosterone Formation in Virilization of the Wolffian Ducts of the Tammar Wallaby,Macropus eugenii

Dihydrotestosterone in androgen target tissues is formed under most circumstances by the 5alpha-reduction of testosterone, but an alternate pathway involves the oxidation of androstanediol to dihydrotestosterone. To investigate the mechanism by which androgens virilize the Wolffian ducts in the tammar wallaby, [(3)H]progesterone was incubated with testes from d 10 and 19 pouch young, and radioactivity was recovered in testosterone and androstanediol at both ages. Analysis of the intermediates indicates that androstanediol was formed both from testosterone via 5alpha-reduction and 3alpha-keto reduction and directly from 5alpha-reduced progestogens. 5alpha-Reductase activity was high in minces of mesonephros/epididymis from d 6-21 pouch young. When minces of urogenital tract tissues from d 19 pouch young were incubated with [(3)H]testosterone, [(3)H]dihydrotestosterone, and [(3)H]androstanediol, dihydrotestosterone was the principal androgen formed in the mesonephros/epididymis, urogenital sinus, and urogenital tubercle, whereas androstanediol was the principal androgen formed by the testis. In intact pouch young studied between d 10 and 34, administration of the 5alpha-reductase inhibitor, 17beta-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5alpha-androstan-3-one, blocked virilization of the Wolffian ducts in males, and administration of androstanediol caused virilization of the Wolffian ducts in females. We conclude that dihydrotestosterone, largely formed in the tissue by the oxidation of androstanediol derived from the testes and also the 5alpha-reduction of testosterone, is responsible for Wolffian duct virilization in this species.

Impairment of epithelial transport but not of barrier function in idiopathic pouchitis after ulcerative colitis

Little is known of the permeability of ileoanal pouches. Hence the aim of the present study was to determine changes in permeability and mucosal function after ileo-pouchanal anastomosis (IPAA) in patients with ulcerative colitis. Biopsies were taken from 43 patients (male:female ratio 28:15; mean age 35.2 (12.5) years) prior to colectomy (ileum prior to pouch), prior to closure of ileostomy (deviation), and after closure of ileostomy (intact pouch) in the case of pouchitis, and from 14 healthy controls. Tissues were mounted in a miniaturised Ussing chamber. Epithelial and subepithelial resistance was determined by transmural impedance analysis. Active Na(+)-glucose cotransport was measured as change in short circuit current after stepwise addition of glucose, and active Cl(-) secretion was measured after stimulation with theophylline and prostaglandin E(2). Neither epithelial resistance nor mannitol fluxes were significantly altered compared with intact controls, indicating no barrier defect in pouchitis. Subepithelial resistances of intact pouches and pouchitis were increased compared with deviation (18.2 (1.6) and 24.3 (1.5) v. 13.6 (1.0) Omegaxcm(2)) consistent with an adaptive thickening of the subepithelial layer. In contrast, active Cl(-) secretion of pouchitis tissues was reduced versus intact pouch and controls (1.4 (0.3) v. 4.3 (0.7) and 4.6 (0.7) micromol/h/cm(2)), and Na(+)-glucose cotransport of pouchitis was reduced compared with intact pouch and controls (1.8 (0.5) v. 4.2 (0.8) and 8.8 (1.3) micromol/h/cm(2)). Ileal mucosa in pouchitis and terminal ileum prior to IPAA exhibit impaired secretory and absorptive transport functions whereas the epithelial barrier function remains unchanged. This differs from findings in ulcerative colitis. Thus the hypothesis that pouchitis represents a remanifestation of ulcerative colitis has to be questioned.

Inhibition of tissue repair by spironolactone: role of mineralocorticoids in fibrous tissue formation.

Mineralocorticoids have been implicated in promoting fibrous tissue formation in various organs. In the present study, we sought to address the potential contribution of mineralocorticoids to fibrous tissue formation using a skin pouch model which has proved valuable for the analysis of inflammatory and wound healing responses. Skin pouches were induced in rats by administration of a phorbol ester, croton oil (0.5 ml of a 1% solution). After 2 weeks, rats were killed and intact pouch tissue collected. Pouch weights of control and aldosterone-treated (0.75 microg/h via osmotic minipump) rats were similar (3.33 +/- 0.44 g vs. 3.70 +/- 0.28 g respectively). However, pouch weights were reduced by more than 50% in spironolactone-treated (25 mg/day powdered in food) animals (1.62 +/- 0.22 g and 1.27 +/- 0.23 g respectively in aldosterone and spironolactone alone groups). To ascertain the effects of different treatments on collagen accumulation, hydroxyproline concentration was measured. Compared with controls, hydroxyproline concentration was significantly reduced following spironolactone treatment (17.1 +/- 0.08 vs. 7.5 +/- 2.0 microg/mg dry wt, respectively, p < 0.01). This response to spironolactone was negated by coadministration of aldosterone (hydroxyproline concentration was 18.6 +/- 2.1 microg/mg dry wt). Following bilateral adrenalectomy, spironolactone reduced pouch weight and hydroxyproline concentration, which was not the case for adrenalectomy alone. Two week aldosterone administration in uninephrectomized rats on high salt diet was deemed ineffective in modulating pouch development (pouch wet wts were 3.48 +/- 0.4 g vs. 3.00 +/- 0.19 g in controls and aldosterone-treated rats, respectively). Mineralocorticoid receptor expression in pouch tissue was demonstrated by RT/PCR. Furthermore, NADP+-dependent 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) activity was detected in pouch tissue, together with lower levels of NAD+-dependent 11beta-HSD2. Spironolactone (p < 0.05) significantly reduced 11beta-HSD1 activity compared with controls. Thus, fibrous tissue possesses requisite components of MC action, and antagonism of mineralocorticoid receptors by spironolactone attenuates its formation. Pouch formation is under the influence of circulating MC and, we would like to propose, is also mediated through corticosteroids generated de novo at the site of tissue repair.

Effect of Chlorhexidine on the Hamster Cheek Pouch: Microcirculation and Penetration Studies

The application of chlorhexidine gluconate on the intact cheek pouch of hamsters led to an immediate increase of flow velocity determined in venules beneath the epithelium. The application of [14C]chlorhexidine on the intact cheek pouch led to accumulation of labeled material in the liver and kidneys. Both findings indicate that penetration of the drug occurred through the epithelium of the cheek pouch.

The effect of neonatal thymectomy on the ontogeny of mitogen responses in the quokka ( Setonix brachyurus)

The lymphocyte responses to phytohaemagglutinin (PHA), Concanavalin A (Con A), and Pokeweed mitogen (PWM) were determined at various intervals throughout pouch life in the quokka ( Setonix brachyurus). The responses to both PHA and Con A of lymphocytes from the blood and mesenteric lymph node of thymectomised pouch young were significantly depressed, indicating that these mitogens stimulate thymus-dependent lymphocytes. In contrast to most other vertebrates, splenic leucocytes from intact pouch young responded poorly to stimulation with these mitogens: after neonatal thymectomy the responses were slightly, but not significantly, depressed. Peripheral blood lymphocytes from thymectomised quokkas showed a significantly decreased responsiveness to PWM at 100 and 140 days of age, but the response of lymphocytes from other sources was not significantly different from that of intact animals at comparable ages. There were no significant trends with age in the mitogen responses of lymphocytes from thymectomised pouch young. These data are discussed in relation to the spontaneous restoration of immune responsiveness which occurs after the end of reserves of immunocompetent lymphocytes which had been built up.

Alterations in secretory patterns following antrectomy in rats with Pavlov pouches.

1. In conscious rats provided with Pavlov pouches, with the antrum retained or resected,the gastric secretory response to various stimuli has been studied. Each acid secretory response was related to that obtained with maximal doses of methacholine and histamine in combination, presumed to reflect the maximal secretory capacity of the mucosa. 2. Three weeks after the operation, the maximal acid secretory capacity was 60 percent lower in the antrectomized than in the intact Pavlov pouch rats; the difference was still larger at 6 weeks and 3-5 months, owing to a gradual increase in the rats with the antrum retained. 3. Antrectomy reduced interdigestive secretion of acid to the same degree as the concomitant reduction in maximal secretory capacity. 4. Acid secretion in response to a maximal infusion of pentagastrin was reduced by about 50 percent at 3 and about 65 percent at 6 weeks after antrectomy. No significant difference was, however, noted between the antrectomized and intact rats when the responses were related to the maximal secretory capacity. The dose response curve to pentagastrin revealed a redcued responsiveness to submaximal doses of this agent following antrectomy. 5. The maximal acid secretory response to histamine was reduced after antrectomy, although the sensitivity to submaximal infusions of histamine appeared to be increased. 6. The mean secretroy output to 2-deoxy-D-glucose was reduced by about 65 percent and that to food by about 85 percent following antrectomy. 7. After antrectomy a background infusion of pentagastrin enhanced the secretory responses to 2-deoxy-D-glucose and to food but did not restore the responses to the levels in the intact rats. The feeding responses as related to the maximal secretory capacity were, however, similar in the two groups on infusing pentagastrin in the antrectomized rats. 8. Interdigestive secretion of pepsin was reduced by about 60 percent after antrectomy, while the peak response to 2-deoxy-Dglucose was about twice the interdigestive level in both groups. Pepsin secretion in response to food showed an increased secretion above the interdigestive level of longer duration in the antrectomized than in the intact Pavlov pouch rats. 9. The irreversibily reduced responsiveness of the gastric mucosa after antrectomy is discussed in relation to known morphological and biochemical changes.

The lymphatic status of hamster cheek pouch tissue in relation to its properties as a graft and as a graft site.

Hamster cheek pouch skin, transplanted to the side of an isogenic host's chest wall, retains its immunologically privileged status as evidenced by the prolonged survival of inlaid homografts of ordinary skin. Various findings sustain the premise that exemption from rejection by otherwise susceptible homografts in both intact pouch tissue and in established pouch skin isografts is due to an impediment in the afferent pathway of the immunologic reflex, i.e., to deficient lymphatic drainage. Although lymphatics were not apparent when dye was injected into pouch skin grafts or into grafts of ordinary skin sustained by them, lymph vessels were readily and consistently revealed by dye injected into intact trunk skin or established isografts of trunk skin. When suspensions of viable lymph node cells from specifically sensitized parental strain donors were injected superficially into either the intact skin or established grafts of normal skin on F(1) hybrid hamsters, a striking hypertrophy of the regional lymph nodes occurred, due to graft-versus-host reactivity. However, similar cell suspensions inoculated into intact pouch tissue or into pouch skin grafts on F(1) hamsters incited no regional lymphadenopathy, indicating the lack of appropriate pathways to the nodes. When skin homografts were inlaid eccentrically into pouch skin isografts, so that they were in contact with host skin at one edge, rejection occurred. Furthermore, rejection of long-established intrapouch skin homografts resulted if the hosts received: (a) small homografts of ordinary skin transplanted to conventional beds; (b) suspensions of donor strain pouch skin epidermal cells, injected intracutaneously; (c) lymph node cells from specifically sensitized donors of the same strain, i.e. adoptive immunization; or, (d) if a portion of the target homograft's perimeter was surgically approximated to body skin. Treatment of normal hamsters with two closely spaced pulses of ALS, although only marginally effective in prolonging the lives of homografts of trunk skin, enabled pouch skin homografts to survive for very long periods. The influence of this brief treatment with immunosuppressant was still demonstrable if challenge of hosts with the weakly immunogenic pouch skin homografts was delayed for 100 days.

MEASUREMENT OF ELECTRICAL POTENTIAL ACROSS INTACT AND ISOLATED POUCH EPITHELIUM OF THE HAMSTER.

MEASUREMENT OF ELECTRICAL POTENTIAL ACROSS INTACT AND ISOLATED POUCH EPITHELIUM OF THE HAMSTER.