Resection Of Proximal Small Intestine Research Articles

Effect of Surgery on Postoperative Levels of the Gut Homeostasis-Regulating Enzyme Intestinal Alkaline Phosphatase.

Intestinal homeostasis is a crucial factor for complication-free short- and long-term postoperative recovery. The brush border enzyme intestinal alkaline phosphatase (IAP) is an important regulator of gut barrier function and intestinal homeostasis and prevents endotoxemia by detoxifying lipopolysaccharides (LPSs). As IAP is predominantly secreted by enterocytes in the duodenum, we hypothesized that pancreaticoduodenectomy (PD) leads to a significantly stronger decrease in IAP than other major abdominal surgery. Pre- and postoperative blood, stool, and intestinal samples were collected from patients undergoing PD, as well as other major surgical procedures without duodenectomy. The samples were analyzed using enzyme histochemistry, the para -nitrophenyl phosphate method for IAP, and the limulus amebocyte lysate assay for LPS. Overall, 88 patients were prospectively enrolled in the study. Fecal IAP activity negatively correlated with serum LPS (r = -0.3603, p = 0.0006). PD led to a significant decline in IAP compared to preoperative baseline levels (p < 0.0001). The decline in IAP correlated with the length of proximal small intestinal resection (r = 0.4271, p = 0.0034). Compared to controls, PD was associated with a much more pronounced reduction in IAP-also after adjusting for surgical trauma (operative time, blood loss; r = 0.4598, p = 0.0086). Simultaneously, PD triggered a clearly more prominent increase in serum LPS compared to controls (p = 0.0001). Increased postoperative LPS was associated with an elongated hospitalization (r = 0.7534, p = 0.0062) and more prominent in pancreatic cancer (p = 0.0009). Based upon the functional roles for IAP, supplementation with exogenous IAP might be a new treatment option to improve short- and long-term outcome after PD.

High occlusion revealing diffuse pneumatosis cystoides intestinalis

Pneumatosis cystoides intestinalis is a rare disorder characterized by the presence of gas-filled cysts in the intestinal wall. It can involve the whole digestive tract, in particular the small intestine and the colon. Diagnosis is based on computed tomography (CT) scan, surgery is performed in patients with complications. We here report a rare case of diffuse pneumatosis cystoides intestinalis resulting in occlusive events requiring surgery. This consisted of resection of proximal small intestine (120 cm) followed by termino-terminal microsurgical anastomosis 5 cm from the duodeno-jejunal flexure.

Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome.

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine peptide that is released in response to luminal nutrients and has unique trophic actions in the gastrointestinal tract. These features suggest GLP-2 may be important in controlling intestinal adaptation. We examined the relationship over time of GLP-2 production and adaptation to intestinal resection, the effects of resection-induced malabsorption on GLP-2 production, and the correlation of endogenous serum GLP-2 levels with adaptation as measured by crypt-cell proliferation (CCP). We initially examined the effect of nutrient malabsorption, induced by a 90% resection of the proximal intestine studied on day 4, on the time course and levels of GLP-2 release. Secondly, the degree of malabsorption was varied by performing intestinal transection or 50, 75, or 90% resection of proximal small intestine. Finally, the relationship of GLP-2 levels over time with adaptation to a 90% resection was examined by determining GLP-2 levels on days 7, 14, and 28, and correlating this with intestinal adaptation, as assessed by morphology and CCP rate. A 90% resection significantly increased basal and postprandial GLP-2 levels, with a net increase in nutrient-stimulated exposure over 90 min; GLP-2 exposure (integrated levels vs. time) increased 12.7-fold in resected animals (P < 0.001). Basal and postprandial GLP-2 levels significantly correlated with the magnitude of intestinal resection (r(2) = 0.71; P < 0.001), CCP (r(2) = 0.48; P < 0.005), and nutrient malabsorption (protein, P < 0.001; fat, P < 0.005). The increase in CCP was maintained to 28 days after small bowel resection and was associated with an ongoing elevation in GLP-2 release. These findings suggest that GLP-2 is important in initiating and maintaining the small intestinal adaptive response to resection.

Autotransplantation Modulates Ileal Enteroendocrine Cell Expression in the Pig

Background. Enteroendocrine cell-derived peptides modulate postresectional small bowel adaptation, which may be attenuated by transplantation. We investigated whether autotransplantation modulates the number and distribution of ileal enteroendocrine cells in pigs with proximal small bowel resection.Materials and methods. Fifteen pigs were assigned into either small intestinal transection or 75% proximal small intestinal resection with or without autotransplantation of the remaining ileum. After 14 weeks the number and subtype distribution of enteroendocrine cells, crypt cell proliferation, and mucosal histology were analyzed from the proximal and distal ends of the remaining ileum.Results. When compared to resected controls, autotransplantation of the ileum decreased the absolute (P < 0.05 in proximal ileum) and proportional (P < 0.05 in distal ileum) crypt enteroendocrine cell number. In addition, autotransplantation reduced somatostatin and glicentin expressing cell counts and abolished the proximodistal gradient of the enteroendocrine cell number. When compared to transected controls, villus height, crypt depth, number of proliferating crypt cells, and crypt cell proliferation index increased after the proximal resection (P < 0.05 in all except in crypt depth and proliferation index of the distal ileum) but remained virtually unchanged after autotransplantation of the ileal remnant.Conclusions. Autotransplantation decreases the crypt enteroendocrine cell number and alters their proximodistal and subtype distribution in the remaining ileum in pigs with proximal small bowel resection. These alterations are associated with attenuated adaptive response of the autotransplanted ileum.

Effect of 50% Small Bowel Resection on Gastric Prostaglandin E 2 Levels in Rats

The mechanism for the production of increased gastric secretion following massive intestinal resection is not clearly defined. The loss of an intestinal inhibitor has been most frequently suggested to explain this hypersecretion. The role of endogenous prostaglandins which can inhibit gastric secretion is not established. The present study was undertaken to determine the effect of 50% proximal small bowel resection on Prostaglandin E 2 (PGE 2) levels in rat gastric mucosa. This study was performed in 30 rats divided into three groups. The first group of rats served as unoperated controls, the second group was sham operated and the third group underwent 50% resection of proximal small intestine. The PGE 2 levels in rat gastric mucosa was decreased significantly (p < 0.001) in the resection group (422.85 ± 7.66 pg/gm) as compared with the sham group (478.77 ± 7.25 pg/gm) and the control group (493.38 ± 4.61 pg/gm). Total gastric acidity was increased significantly (p llt 0.001) in the resection group (63.05 ± 2.64 mEq/L) as compared with the sham group (15.21 ± 0.99 mEq/L) and the control group (17.19 ± 0.80 mEq/L). The PGE 2 levels and total gastric acidity were not significantly changed in either the control or sham operation groups (p > 0.05). The results suggest that endogenous prostaglandin synthesis has a regulatory role in gastric hyperacidity after 50% proximal small bowel resection in rats.

Effect of ileal autotransplantation on cholesterol, bile acids, and biliary lipids in pigs with proximal small bowel resection

Our major aim was to investigate the consequences of ileal autotransplantation in pigs with proximal small intestinal resection on biliary lipids and metabolism of bile acids. Biliary lipid secretion rates and bile acid absorption were assessed by measuring dietary and biliary lipids, fractional cholesterol absorption, and fecal excretion of cholesterol and bile acids. In addition, serum bile acids and cholesterol, biliary and fecal bile acid species, and ileal villus height were determined after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum with systemic venous drainage (n = 15) or transection (n = 5). Autotransplantation further increased fecal excretion of neutral and acidic steroids and serum concentration of bile acids after proximal resection (P < .05 for all); autotransplantation significantly decreased serum cholesterol, ileal villus height, fractional bile acid and cholesterol absorption, and biliary molar percentage of total and primary bile acids, whereas biliary secretion of bile acids, enriched by secondary bile acids, and cholesterol remained unchanged. At 14 weeks, ileal villus height, fractional bile acid and cholesterol absorption, biliary molar percentage of bile acids, and proportion of secondary biliary bile acids were altered by transplantation from the respective postresection values of 864 +/- 22 microm, 97.9 +/- 0.6%, 26.9 +/- 3.9%, 91.8 +/- 1.2% and 9.2 +/- 1.3% to 428 +/- 21 microm, 91.1 +/- 1.5%, 9.5 +/- 1.1%, 83.9 +/- 1.4% and 52.5 +/- 3.5% (P < .005 for all). Posttransplantation biliary bile acid secretion correlated positively with fractional reabsorption (r = .70) and biliary molar percentage (r = .73) of bile acids and ileal villus height (r = .65; P < .01 for all). Decreased absorption efficiency and biliary molar percentage of bile acids, increased biliary secondary bile acids, and short ileal villi point to bacterial overgrowth-induced bile acid malabsorption, which with decreased absorptive area may contribute to malabsorption of other lipids after ileal autotransplantation. Compensatory increase in cholesterol synthesis in the pigs with autotransplanted ileum appeared sufficient for constant biliary secretion of cholesterol and bile acids.

Analysis of cloned cDNAs differentially expressed in adapting remnant small intestine after partial resection.

After partial resection, the remnant small intestine undergoes an adaptive response. Little is known about the molecular and cellular basis of intestinal adaptation. To identify genes transcriptionally regulated in response to loss of functional bowel surface area, we have isolated cDNAs differentially expressed in the adaptive ileum 48 h after 70% proximal small intestinal resection. A cDNA library constructed from the remnant ileum of rats subjected to resection was screened using subtractive hybridization techniques. Several groups of cDNA clones that were induced during intestinal adaptation were isolated. The first included liver fatty acid binding protein, apolipoprotein A-IV, cellular retinol binding protein II, and ileal lipid binding protein. These all encode proteins involved in the absorption, metabolism, and trafficking of nutrients. A second group included the catalytic subunit of protein phosphatase 1 delta, a 78-kDa glucose-regulated protein (grp 78; a glucose-regulated member of the 70-kDa heat-shock protein family), and several pancreatitis-associated proteins. A third group of induced genes contained novel cDNAs. To better characterize the adaptive response, the temporal, spatial, and cellular patterns of expression of several of these genes were analyzed with the use of immunohistochemical and in situ hybridization techniques. These studies indicate that during early adaptation, genes involved in nutrient trafficking, protein processing, and cell cycle regulation are transcriptionally regulated in the residual small intestine in distinct temporal and regional patterns consistent with a complex multifaceted response to intestinal resection.

Expression of mRNA for vasoactive intestinal peptide in rat small intestine

Transplantation of small intestine is a neural model that permits studies of expression of the neuropeptide, vasoactive intestinal peptide, following extrinsic denervation, transection of intrinsic neural pathways, and an ischemic interval. Tissue levels of vasoactive intestinal peptide were examined at 3 months in ileum from a sham operation, in ileum after resection of proximal small intestine, in ileum after resection of proximal small intestine and extrinsic denervation, in ileum after resection of proximal small intestine and 30 min of ischemia, and in ileum obtained 3 months after ileal isografting in Lewis-to-Lewis combinations. Vasoactive intestinal peptide levels were increased in transplanted rat ileum, resection controls, denervation controls, and ischemic controls compared to sham-operated ileum (pANOVA < 0.01). The increased levels of this peptide were highest in denervation controls and lowest in ischemic controls. Northern blot analysis using rat vasoactive intestinal peptide cDNA identified a single 1.7-kb transcript in normal and transplanted rat ileum. The density of vasoactive intestinal peptide transcripts was increased in transplanted ileum (8450 ± 540) compared to normal ileum (5790 ± 620) ( P < 0.01), and the ratio of this transcript to glyceraldehyde-3-phosphate dehydrogenase density units was also increased in transplanted ileum (0.81 ± 0.08) compared to normal ileum (0.40 ± 0.07; P < 0.01). Enhanced transcriptional regulation was the likely mechanism for increased tissue vasoactive intestinal peptide. The increased tissue levels appeared to be a response to extrinsic denervation and transection of intrinsic neural pathways, while an ischemic interval appeared to decrease tissue levels of the peptide.

Adaptation of cholesterol absorption after proximal resection of porcine small intestine.

Cholesterol absorption occurs primarily in the upper small intestine. Our aim was to assess absorption of cholesterol during ileal adaptation after proximal small intestinal resection. In vivo absorption and elimination of cholesterol, plasma cholesterol, cholesterol precursors, and plant sterols were related to intestinal morphology and transit 4 (n = 5), 8 (n = 5), and 14 (n = 5) weeks after a 75% proximal resection of porcine small intestine, and compared to preoperative (n = 5) and transected (n = 5) control animals. Fractional cholesterol absorption, the daily amount of cholesterol absorbed, plasma cholesterol, and plant sterol to cholesterol proportions were significantly (P < 0.05 or less) decreased, whereas fecal loss of cholesterol as neutral steroids, less so as bile acids, plasma cholesterol precursor proportions, and ileal mass and villus height were significantly increased (P < 0.05 or less) after 8 weeks of the resection. Cholesterol absorption efficiency, decreased by the resection, was gradually increased from 5.4 +/- 2.2 to 26.9 +/- 3.9% during the 14 postoperative weeks (P < 0.0001) simultaneously with a 46% increase in villus height compared with transection (P < 0.0001), but absorption remained still below control levels (80.4 +/- 2.5%, P < 0.0001). In resected and control animals, villus height correlated positively with cholesterol absorption efficiency (r = 0.85, P < 0.0001; r = 0.76, P = 0.01) and plasma plant sterol proportions (r = 0.94-0.95, P < 0.0001; r = 0.78-0.85, P < 0.008), respectively. In conclusion, after massive proximal small bowel resection, adaptation of intestinal cholesterol absorption efficiency occurs in the distal ileum closely parlleling villus hypertrophy.

Ion transport in the experimental short bowel syndrome of the rat

The adaptational changes of epithelial ion transport in the short bowel syndrome were studied. Ileal remnants of rats were investigated 8 weeks after 70% proximal small intestinal resection. Pure epithelial resistance measured by impedance analysis decreased from 27 ± 1 to 21 ± 1 Ω · cm2, and polyethylene glycol 4000 fluxes increased from 2.5 ± 0.3 to 3.6 ± 0.3 nmol · h−1 · cm−2, indicating increased permeability of the short bowel. Unidirectional flux measurements in control ileum showed absorptive net fluxes of Na+ and Cl− that were assigned to electroneutral NaCl absorption and a short-circuit current that was accounted for by the residual flux (HCO3− secretion). Neither NaCl absorption nor HCO3− secretion were altered in the short bowel. Also, electrogenic Cl− secretion, defined after maximal stimulation by theophylline and prostaglandin E1 was not changed in the short bowel. In contrast, electrogenic Na+/glucose cotransport increased in Vmax from 2.0 ± 0.3 in controls to 5.0 ± 1.0 μmol · h1 · cm−2 in the short bowel. Tight junction structure was studied by freeze-fracture electron microscopy. The number of horizontal strands was unchanged, whereas tight junction depth was slightly increased in the short bowel. Microvillus area of short bowels was increased by 20% in villus regions. Under the light microscope, villus height was increased by 30%. In conclusion, the short bowel mucosa undergoes adaptive responses to reduced overall absorptive area by increasing glucose-dependent electrogenic Na+ absorption to 250%, which is partly caused by increased villus and microvillus surface area. Electrogenic Cl− and HCO3− secretion and electroneutral NaCl absorption remained unchanged. The decreased epithelial resistance is caused by mucosal surface amplification.

Adaptation of Epithelial Ion Transport in the Short Bowel Syndrome

Ileal remnants 8 weeks after 70% proximal small intestinal resection were used as a model for the short bowel syndrome in man. For comparing active ion transport between control ileum and short bowel with the Ussing technique, the relative contribution of the subepithelial resistance has to be considered. Epithelial/subepithelial voltage divider ratios were determined in the Ussing chamber by positioning the tip of a microelectrode just below the epithelium. In control ileum, the ratio of total to epithelial voltage deflection was 1:0.56 +/- 0.03 (n = 48) and decreased to 1:0.42 +/- 0.01 (n = 67; p less than 0.001) under the short bowel condition. Thus, the factors by which a measured short-circuit current (Isc) underestimates the true electrogenic transport was 1.78 +/- 0.09 (n = 48) in control ileum and 2.36 +/- 0.08 (n = 67; p less than 0.001) in the short bowel. Glucose-dependent electrogenic Na absorption was defined using bathing media containing 48 mM 3-o-methyl-glucose as the decrease in Isc (delta Isc) after addition of 0.5 mM phlorizin. After correction for the respective contributions of the subepithelial resistance, delta Isc was -1.4 +/- 0.2 microEq.h-1.cm-2 (n = 13) in control ileum and -3.2 +/- 0.7 microEq.h-1.cm-2 (n = 11; p less than 0.01) in the short bowel. We conclude that the mucosa in the short bowel syndrome is characterized by an increase in glucose-dependent electrogenic Na absorption, probably as an adaptive response to the reduced overall absorptive area of the remaining intestine.

Sodium-dependent D-glucose transport after proximal small intestinal resection in rat.

Massive small intestinal resection results in both structural and functional changes in the residual small bowel. Sodium-dependent D-glucose transport was examined in brush-border membrane vesicles derived from the terminal 20-30 cm of ileal mucosa of male Sprague-Dawley rats, 2 and 6 wk after 66% proximal jejunoileal resection or jejunoileal transection. Kinetic characteristics for sodium-dependent D-glucose transport were investigated with rapid filtration under conditions of a zero-trans, 100 mM cis-NaSCN gradient. Mucosal weight, protein, and DNA content were increased in the residual terminal intestinal segment compared with transected controls, whereas morphometric studies revealed increased villus and crypt heights as well as an increased mitotic index. Mean kinetic transport parameters at 6 wk after proximal small bowel resection revealed two saturable systems in the distal residual ileum: first, a low-affinity, high-capacity system with a Km of 0.19 +/- 0.03 mM and a Vmax of 0.48 +/- 0.04 nmol.mg protein-1.min-1; and second, a high-affinity, low-capacity system with a Km of 0.009 +/- 0.001 mM and a Vmax of 0.105 +/- 0.016 nmol.mg protein-1.min-1. In contrast, negligible sodium-dependent D-glucose transport was detected in the most distal ileum in control animals or animals 2 wk after resection or 2 and 6 wk after transection. Thus adaptational changes including mucosal hyperplasia and the appearance of two sodium-dependent D-glucose brush-border membrane vesicle transport systems occur in the residual distal intestine after massive proximal small bowel resection.

Neurotensin-like immunoreactivity after intestinal resection in the rat.

Neurotensin is a tridecapeptide located mainly in the distal small intestine. The present study was carried out in order to investigate the neurotensin response after proximal small intestinal resection in the rat. After resection, the median plasma concentration of neurotensin like immunoreactivity (NTLI) was unchanged compared with sham operated rats. Intragastric instillation of fat increased the plasma concentration of NTLI from 45 pmol/l (34-63) in sham operated rats to 92 pmol/l (46-121) in resected rats. No significant increase in the plasma concentration of NTLI was found after intragastric instillation of amino acids or glucose. The tissue concentration of NTLI increased significantly in the jejunum and ileum after proximal small intestinal resection, while the number of immunoreactive neurotensin cells was unchanged. This study shows that the adaptive responses in the distal small intestine after proximal small intestinal resection also involve the neurotensin producing cells.

Amino acid and peptide absorption after proximal small intestinal resection in the rat.

In experimental animals with massive proximal intestinal resection, in vivo ileal absorption of an amino acid mixture containing L-leucine and glycine as well as two different dipeptides, L-leucyl-glycine and glycyl-L-leucine, were compared. Both amino acid and dipeptide absorption were markedly enhanced in the ileal segments. However, the absorption rates from the two perfused dipeptides differed. L-leucine absorption from L-leucyl-glycine was much greater than from glycyl-L-leucine. Brush border amino-peptidase activities after resection were also increased but dissociation between absorption and hydrolytic activity occurred. This study indicates that certain dipeptides are handled differently by adapting ileal segments. Furthermore, the changes observed probably reflect mucosal cellular hyperplasia occurring in association with intestinal adaptation.

Abolishment of Oral Trypsin Inhibitor Stimulation of the Rat Exocrine Pancreas after Duodeno-jejunal Resection

The effect of long-term oral trypsin inhibitor administration on the exocrine pancreas was studied in unoperated rats and in rats operated on by a 30% proximal small intestinal resection. The following observations were made: in unoperated rats sacrificed 18 hours after the last trypsin inhibitor ingestion there was an increase of the wet weight of pancreas, increase of the pancreatic protein, and an increase of pancreatic and intestinal trypsin(ogen) and of pancreatic amylase by comparison with the controls. In operated rats, treated and examined in an identical way, no influences on the exocrine pancreas were found. It is suggested that the abolishment of the trypsin inhibitor effects on the exocrine pancreas in operated rats reflects the removal of the site of production of one or more intestinal hormone(s) or factor(s) responsible for these effects. In unoperated rats examined 4 hours after the last trypsin inhibitor ingestion a reduction of the pancreatic trypsinogen and amylase and an increase of the intestinal amylase were found, indicating a secretory response of the pancreas to the intraluminal trypsin inhibitor; the low values of intestinal trypsin found in these rats probably reflect inhibition of rat trypsin by the bovine lung trypsin inhibitor.