Karen D. Libsch

Pediatric ileal pouch-anal anastomosis: functional outcomes and quality of life.

BACKGROUND/PURPOSE The aim of this study was to assess and correlate functional outcomes and surgical results with health-related quality of life after ileal pouch-anal anastomosis (IPAA) in pediatric patients. METHODS Functional outcome was determined by questionnaire and telephone interview. Surgical results were determined by retrospective chart review. RESULTS Data were gathered from 26 patients (mean age at IPAA, 12 years; mean follow-up, 3.7 years). Diagnoses were ulcerative colitis in 18, indeterminate colitis in 4, and familial polyposis in 4. Indications for IPAA included intractability, medication toxicity, growth delay, and cancer prophylaxis. Short-term complications (5 patients; 19%) included partial small bowel obstruction, stomal revision, pouch abscess, and negative exploration. Long-term complications (8 patients; 31%) were chronic pouchitis and anal stricture. The average number of stools per 24 hours was 3.9. No incontinence was reported; dietary restrictions were negligible. Although there were minimal differences from population norms, parental anxiety remained high. Chronic pouchitis correlated negatively with physical summary score. Nocturnal stooling negatively affected psychosocial quality of life. CONCLUSIONS Pediatric IPAA resulted in excellent bowel health. Quality of life, physical function, mental health, and self-esteem were equivalent to those of healthy children. These data may help families and physicians make informed surgical decisions.

Intraductal papillary mucinous neoplasm: did it exist prior to 1980?

Introduction Intraductal papillary mucinous neoplasm (IPMN) of the pancreas was first reported in 1982. It is not clear whether the appearance of this neoplasm is a new epidemic or an old disease previously overlooked. Aim To determine whether IPMN existed as a separate entity before 1982. Methodology We reviewed our pathology reports from all cases of pancreatic cancer diagnosed between 1960 and 1980. Pathologic specimens with descriptors—“mucinous,” “cystic,” or “papillary”—underwent histologic reexamination. Medical records for patients given a new diagnosis of IPMN from this pathologic review were assessed. Results Eighty-four of more than 4,000 pathology reports reviewed contained a key word triggering histologic review. IPMN was identified in 21 patients. Patients had a mean age of 63 years (range, 44–77 years) with symptoms present for a mean of 76 months (median, 15 months; range, 1–516 months). Reported symptoms were abdominal pain in 17, jaundice in 13, weight loss in 12, and pancreatic insufficiency in 7 patients. On pathologic review, the in situ component was graded as adenoma in 4, borderline in 4, and carcinoma in 13. Parenchymal invasion was present in 11/21 (52%). Excluding four postoperative mortalities, mean time to death was 58 months (median, 15 months; range, 2–264 months). Seven patients died of IPMN, 4 of other causes without evidence of recurrence, and 6 of unknown causes. Conclusions IPMN existed in its current known form prior to 1982. Our study cannot determine whether the prevalence or incidence has changed since that time.

Canine Ileal Motor Activity after a Model of Jejunoileal Autotransplantation

ObjectiveTo determine mechanisms by which extrinsic innervation to the jejunoileum controls ileal motility. Summary Background DataSmall bowel transplantation is complicated by diarrhea and delayed gastric emptying, possibly secondary to altered motility. Ileal motility after small bowel transplantation is poorly characterized. MethodsMotor activity was recorded from four dogs during fasting and after feeding small (64 Kcal) or large (256 Kcal) meals. Short-chain fatty acids known to induce unique ileal motor patterns were administered into the distal ileum during fasting. Dogs were studied before and after jejunoileal denervation simulating autotransplantation. ResultsAfter jejunoileal denervation, the ileal migrating motor complex (MMC) persisted but was no longer temporally coordinated with duodenal MMCs. Spontaneous giant migrating contractions occurred more frequently after denervation and more commonly originated proximally in the jejunum, but the velocity of migration did not differ. In contrast, the incidence and characteristics of spontaneous discrete clustered contractions (DCCs) did not differ. Short-chain fatty acids reproducibly initiated giant migrating contractions and discrete clustered contractions in the distal ileum without differences before and after denervation. Large but not small meals inhibited the ileal MMC after denervation. ConclusionsExtrinsic innervation and/or intrinsic neural continuity with the duodenum and/or colon control temporal coordination of ileal motility with the duodenum and modulate postprandial inhibition of fasting motility and presence of giant migrating contractions. These changes in motility patterns may prove important in mediating enteric dysfunction after small bowel transplantation.

Role of extrinsic innervation in jejunal absorptive adaptation to subtotal small bowel resection: A model of segmental small bowel transplantation

Segmental small bowel transplantation offers theoretic advantages over total jejunoileal transplantation, but the regional ability of the transplanted segment to adapt is unknown. Absorption was measured in an 80 cm jejunal segment via a triple-lumen perfusion technique. Separate experiments measuring absorption of four nutrients (glucose, glutamine, oleic acid, and taurocholic acid) were performed before and 2 and 12 weeks after operative intervention. Control dogs (CON, n = 6) underwent distal 50% enterectomy. Experimental dogs (EXT DEN, n = 6), in addition to resection, underwent complete extrinsic denervation of the remaining jejunum. All dogs developed diarrhea, which rhesolved in all CON dogs but persisted in all EXT DEN dogs. Maximal weight loss was greater in the EXT DEN group. Glucose and oleate absorption was decreased 2 weeks after ileal resection in both the CON and EXT DEN dogs; glutamine absorption was decreased at 2 weeks in EXT DEN dogs only. Taurocholate and water absorption remained unchanged in both groups. Absorption of all solutes returned to baseline at 12 weeks in both groups. Despite greater weight loss and persistent diarrhea in EXT DEN dogs, at 12 weeks there were no differences in net absorptive fluxes between the EXT DEN and the CON group after extrinsic denervation. The extrinsic denervation necessitated by small bowel transplantation does not appear to blunt the net jejunal adaptive response to total ileal resection, but may temporarily alter glutamine absorption.

Differential adrenergic response to extrinsic denervation in canine longitudinal jejunal and ileal smooth muscle.

Early postoperative complications after small bowel transplantation (SBT) are likely mediated, at least in part, by dysmotility caused by the obligate disruption of extrinsic and enteric nerves in the graft. Adrenergic hypersensitivity of gut smooth muscle has been observed in some (but not all) segments of intestine in various experimental models of SBT, highlighting regional and species variability in response to denervation. Little is known about changes in canine longitudinal muscle after extrinsic denervation. Six dogs each underwent either complete extrinsic denervation of the jejunoileum or a control operation (transection and reanastomosis of the proximal jejunum and distal ileum). In vitro contractile response of longitudinal muscle strips to norepinephrine was evaluated at the time of the operation, and 2 weeks and 8 weeks later. After extrinsic denervation, the jejunal response to norepinephrine was preserved at all time points; however, the ileum displayed a decreased sensitivity to norepinephrine, an effect unmasked after intramural neural blockade with tetrodotoxin. These data support a potential for neurally mediated dysmotility after SBT and reinforce the differences in responses to extrinsic denervation between species, as well as differences within different regions and between anatomic segments of small intestine in the same species.

Extrinsic denervation alters postprandial absorption of glucose and glutamine in the ileum: implications for small bowel transplantation.

In the postprandial period, augmentation of absorption of water, electrolytes, and taurocholate is believed to occur in the ileum. The role of extrinsic innervation in this postprandial augmentation has not been well studied and may be an important concept in small bowel transplantation. Our aim was to investigate extrinsic neural mechanisms mediating postprandial absorptive patterns. The study hypothesis was that postprandial augmentation of absorption in the ileum is blunted in transplanted (extrinsically denervated) bowel. Ileal absorption was studied in six dogs with an 80-cm in situ ileal segment via a triple-lumen perfusion technique using an iso-osmolar, ileal-like electrolyte solution alone and containing either glucose 2.5 mM, glutamine 2.5 mM, oleic acid 5 mM, or taurocholate 5 mM. Net absorptive fluxes of each substrate, as well as water and electrolytes, were measured in both the fasted state and after a 400-Kcal mixed meal before and at 2 and 12 weeks after our validated model of complete extrinsic denervation of the jejunoileum. At baseline, there were no differences in absorption of water, electrolytes, or any nutrient postprandially compared with the fasted state. Two weeks after extrinsic denervation, absorption of glucose at both 1 and 2 hours postprandially was decreased compared with absorption during fasting. Glutamine absorption was also decreased at 2 hours postprandially. At 12 weeks after extrinsic denervation, net postprandial absorption of glucose and glutamine returned toward normal and was not different from fasting absorption. No differences were noted in postprandial absorption of oleic acid or taurocholate at any time point. Decreases in absorption of nutrients postprandially after extrinsic denervation (which is necessitated by small bowel transplantation) may play an important role in post-transplant enteric absorptive dysfunction. The previously described postprandial augmentation in net absorption may be a function of enterically isolated gut and does not appear to occur in the in situ ileum.

Postprandial absorptive augmentation of water and electrolytes in the colon requires intraluminal glucose.

Postprandial absorptive augmentation of water and electrolytes occurs in the small intestine and colon. The role of intraluminal nutrients in this response is poorly understood. Our aim was to determine whether postprandial absorptive augmentation of water and electrolytes in the colon requires the presence of intraluminal glucose. Four adult dogs underwent enteric isolation of a 50 cm segment of proximal colon. An ileal-like electrolyte solution (Na+, 130 mEq/L; K+, 10 mEq/L; Cl-, 115 mEq/L; and HCO3-, 25 mEq/L), alone or containing glucose (10 mmol/L), was infused at 4 ml/min into the colonic segment. Experiments were performed during fasting and postprandially after a 400 Kcal mixed-nutrient meal. Effluent was collected in 60-minute intervals after steady state was achieved. Net absorptive flux of water was increased in the presence of intraluminal glucose during the fasted state (11 ± 0.8 vs 7.4 ± 0.9 µl/min/ cm, P < 0.01). The net absorptive flux of water and electrolytes increased postprandially only in the presence of intraluminal glucose (P < 0.05). Our finding that glucose augments both baseline and postprandial absorption of water and electrolytes in the proximal colon suggests that luminal factors have a role in postprandial absorptive augmentation. Whether this is specific to glucose or occurs with other nutrients remains to be determined.

Extrinsic denervation causes a transient proabsorptive adrenergic hypersensitivity in the canine proximal colon.

Our aim was to determine if extrinsic denervation alters the absorptive response of the colon to proabsorptive and prosecretory stimuli. Ten dogs underwent enteric isolation of a 50-cm proximal colonic segment; five were also randomized to undergo extrinsic denervation (DEN). At 2 and 13 wk postoperatively, net absorptive fluxes (mean ± sem) of water and electrolytes were determined during basal conditions and during proabsorptive low-dose (0.3 μg/kg/min) or high-dose (3 μg/kg/min) norepinephrine or prosecretory VIP (500 pg/kg/min). The net absorptive flux of water under basal conditions was decreased in DEN versus neurally intact controls at two weeks (4.0 ± 0.6 vs 6.6 ± 0.7 μl/min/cm, P = 0.03) but did not differ at 13 weeks (5.0 ± 1.0 vs 5.7 ± 0.9, P > 0.05). Low- and high-dose norepinephrine increased water absorption in both groups at two weeks; the change in flux for high-dose norepinephrine was greater in DEN versus controls (4.1 ± 1 vs 2.1 ± 0.6 μl/min/cm, P = 0.04). Net absorptive fluxes of Na+ and Cl− followed these trends. VIP did not alter absorption of water or electrolytes. Extrinsic denervation of the proximal colon causes a decrease in net colonic absorption and a transient, proabsorptive adrenergic hypersensitivity in colonic absorption of water and electrolytes. VIP does not have a net secretory effect in the proximal canine colon.

Postprandial Augmentation of Absorption of Water and Electrolytes in Jejunum Is Neurally Modulated: Implications for Segmental Small Bowel Transplantation

Postprandial augmentation of absorption of water and electrolytes is believed to occur in the jejunum. Neural mechanisms of control, however, have not been studied in the in situ jejunum or in the transplanted bowel. The aim of this study was to determine if postprandial augmentation of absorption occurs in the in situ jejunum and to evaluate neural mechanisms controlling postprandial jejunal absorption. Based on our previous work, we hypothesized that postprandial augmentation of absorption does not occur in the jejunum in situ and that extrinsic denervation of the jejunum is associated with decreased postprandial absorption. Absorption was studied in an 80 cm, in situ jejunal segment in six dogs by using an isosmolar electrolyte solution alone, or with 80 mmol/L glucose before and after jejunal transection to disrupt intrinsic neural continuity of the study segment with the remaining gut. Net absorptive fluxes of water and electrolytes were measured in the fasted state and after a 400-kcal meal. Another six dogs were studied 3 weeks after our validated model of extrinsic denervation of jejunoileum; identical fasting and postprandial absorptive states were evaluated. Postprandial augmentation of absorption of water and electrolytes did occur in the jejunum (P<0.03) both in the absence and in the presence of intraluminal glucose. After intrinsic neural transection or extrinsic denervation, no postprandial augmentation of absorption occurred, with or without glucose. Postprandial augmentation of absorption of water and electrolytes occurs in the in situ jejunum. Disrupting intrinsic neural continuity or extrinsic denervation (as after intestinal transplantation) abolishes postprandial augmentation.

Small Bowel Extrinsic Denervation Does Not Alter Water and Electrolyte Absorption From the Colon in the Fasting or Early Postprandial State

Small bowel transplantation (SBT) causes watery diarrhea. The decreases shown previously in absorption of water, electrolytes, and bile salts in the jejunum and ileum, although present, are not dramatic and seem not to be great enough to explain the diarrhea. Our aim was to determine changes in water and electrolyte absorption in the colon during fasting and postprandially in a canine preparation of jejunoileal extrinsic denervation, which serves as a model of jejunoileal autotransplantation. We hypothesized that colonic absorption of water and electrolytes decreases transiently in the colon after SBT. Six dogs had cannulas implanted in the colon to study absorption of an ileal-like basal electrolyte solution with or without 10 mmol/L glucose. Absorption during fasting and postprandially was measured before and 2 and 12 weeks after a validated preparation of jejunoileal extrinsic denervation. All dogs developed diarrhea after SBT. Net colonic absorptive fluxes of water and electrolytes in the colon did not change from baseline values at 2 or 12 weeks after extrinsic denervation, either during fasting or postprandially; glucose in the infusate did not alter absorptive fluxes during fasting or postprandially. Extrinsic denervation of the small intestine does not appear to alter colonic absorption of water or electrolytes during fasting or postprandially. These observations suggest that the neurally intact colon has a minimal role in the diarrhea after SBT.