Nicholas J. Zyromski

Duodenal carcinoid tumors: how aggressive should we be?

Duodenal carcinoid tumors are uncommon. It is not known whether they behave more like carcinoid tumors in the appendix (indolent course) or those in the ileum (often virulent)—crucial information for determining tbe need for radical resection. A retrospective review at our tertiary referral center (from 1976 to 1999) identified 27 patients with primary duodenal carcinoid lesions, excluding functional islet cell tumors. Endoscopic biopsy provided tbe diagnosis in 78% of patients. Treatment was by endoscopic excision (n = 11), transduodenal excision (n = 8), pancreaticoduodenectomy (n = 3), segmental distal duodenectomy (n = 2), or palliative operation (n = 2). One patient did not undergo operation because of comorbidity. Eighteen of 19 patients with tumors smaller than 2 cm remained disease free after local (endoscopic or transduodenal) excision. The exception was a patient with a small periampullary carcinoid lesion. In contrast, all four patients with carcinoid tumors 2 cm or larger who were resected for cure developed a recurrence (2 to 9 years postoperatively). We conclude that duodenal carcinoid tumors smaller than 2 cm may be excised locally; to ensure complete resection we recommend open transduodenal excision for tumors between 1 and 2 cm. Endoscopic follow-up is indicated. It is unclear whether patients with larger tumors benefit from more aggressive locoregional resection. Ampullary/periampullary carcinoid tumors should be considered separately, as their behavior is unpredictable.

Necrotizing pancreatitis caused by pancreatic ductal adenocarcinoma

Severe acute necrotizing pancreatitis occurs in 3%–5% of all patients with acute pancreatitis. Adenocarcinoma of the pancreas rarely causes acute pancreatitis (1), and we were unable to find any reports of acute necrotizing pancreatitis caused by pancreatic ductal adenocarcinoma. Our recent experience with a patient who developed severe necrotizing pancreatitis secondary to pancreatic adenocarcinoma highlights this association. Because of the rarity of this relationship, we do not advocate aggressive attempts to identify underlying malignancy in all patients with necrotizing pancreatitis of unclear etiology.

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.

Limitations of implantable, miniature ultrasonic transducers to measure wall movement in the canine jejunum

BACKGROUNDnWe used implantable miniature ultrasonic transducers to measure longitudinal distance, circumference, and wall thickness dynamically in vivo in canine jejunum. We hoped to differentiate circular from longitudinal smooth muscle contractions and to correlate physical measurements of change in distance within the jejunal wall with intraluminal manometry.nnnMATERIALS AND METHODSnIn acute experiments at the time of celiotomy, longitudinal distances, circumferences, and wall thickness were measured directly and by ultrasonic transducers sewn to serosa and mucosa. Measurements were obtained with the intestine empty and after distention with air, water, or semisolid slurry. In chronic in vivo experiments in conscious dogs with indwelling ultrasonic transducers and intraluminal manometers, sonometric dimensions were correlated with manometric recordings. In acute experiments, sonometric measurements were similar to direct measurements. In chronic experiments in vivo, smallest ultrasonometric measurements of circumferences of the jejunum correlated in a phase-locked temporal manner with both highest intraluminal pressures and greatest wall thickness.nnnRESULTSnLongitudinal distances increased during decreases in circumference. Distances orad to the site maximal intraluminal pressure peaked at 0.58 +/- 0.04 s ( x +/- SEM) before, and those aborad to this point 0.42 +/- 0.04 s after attaining minimum circumferences.nnnCONCLUSIONSnUltrasonic crystals can monitor geometric changes in the bowel wall with certain limitations, especially when obtained in vivo. Contraction of circular and longitudinal muscles, although phase-locked, do not appear to occur exactly synchronously in canine jejunum.

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.

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.