Small Bowel Surface Research Articles

Small Bowel Obstruction as a Rare Complication of Progressive Sclerosing Mesenteritis

Abstract Introduction/Objective Sclerosing Mesenteritis is an uncommon, idiopathic, localized inflammatory syndrome involving the small intestine and colonic mesentery. It is considered a benign condition that commonly occurs in elderly with a gender predilection for males, and its etiology remains unknown. Small Bowel Obstruction (SBO) is a rare, unexpected, but detrimental complication of progressive Sclerosing Mesenteritis. Herein, we present a case of an enlarging, progressive Sclerosing Mesenteritis with extensive involvement of the small bowel and mesentery requiring two consecutive major surgical interventions. Methods/Case Report A 72-year-old male with Myelodysplastic Syndrome (MDS) and recent history of loop ileostomy due to distal intestinal obstruction secondary to enlarging Sclerosing Mesenteritis, presented to our institution with non-specific symptoms of worsening abdominal pain and multiple episodes of gastrointestinal bleeding. Radiographic investigation revealed SBO and he subsequently underwent exploratory laparotomy resulting in total enterectomy with excision of mesenteric mass, extended right colectomy, Whipple procedure, and gastrostomy. The specimens were sent to pathology for histopathological evaluation and gross examination revealed several bosselated, tan-white, firm and rubbery, fibrotic lesions with associated lobulated fibroadipose tissue. Microscopic examination showed extensive mesenteric fibrosis with dense bundles of collagen fibers, areas of fat necrosis, mucosal ischemia and calcification involving the small bowel and serosal surface of large intestine and peritoneum. The lesional cells showed minimal atypia, mitoses, and lacked the Beta-catenin nuclear staining seen in mesenteric fibromatosis. Given the clinical history and histopathological findings of the lesion, we favored the diagnosis of Sclerosing Mesenteritis. Results (if a Case Study enter NA) N/A Conclusion The etiology of Sclerosing Mesenteritis is not well-understood and there are cases of Sclerosing Mesenteritis reported in the literature in association with trauma, surgery, malignancy, and IgG4-related disease. Our patient’s post-operative history was complicated by short gut syndrome, and he is currently requiring small bowel transplant. We report this case for its unusual and aggressive clinical presentation, and to heighten clinical awareness for detrimental consequences of this seemingly benign condition.

Stem cell and niche regulation in human short bowel syndrome.

Loss of functional small bowel surface area following surgical resection for disorders such as Crohn’s disease, intestinal ischemic injury, radiation enteritis, and in children, necrotizing enterocolitis, atresia, and gastroschisis, may result in short bowel syndrome, with attendant high morbidity, mortality, and health care costs in the United States. Following resection, the remaining small bowel epithelium mounts an adaptive response, resulting in increased crypt cell proliferation, increased villus height, increased crypt depth, and enhanced nutrient and electrolyte absorption. Although these morphologic and functional changes are well described in animal models, the adaptive response in humans is less well understood. Clinically the response is unpredictable and often inadequate. Here we address the hypotheses that human intestinal stem cell populations are expanded and that the stem cell niche is regulated following massive gut resection in short bowel syndrome (SBS). We use intestinal enteroid cultures from patients with SBS to show that the magnitude and phenotype of the adaptive stem cell response are both regulated by stromal niche cells, including intestinal subepithelial myofibroblasts, which are activated by intestinal resection to enhance epithelial stem and proliferative cell responses. Our data suggest that myofibroblast regulation of bone morphogenetic protein signaling pathways plays a role in the gut adaptive response after resection.

X-ray microtomography is a novel method for accurate evaluation of small-bowel mucosal morphology and surface area

The often poorly orientated small-bowel mucosal biopsies taken for the diagnostics of celiac disease and other intestinal disorders are prone to misinterpretation. Furthermore, conventional histopathology has suboptimal sensitivity for early histopathological changes observed in short-term challenge studies. X-ray microtomography (micro-CT) is a promising new method for accurate imaging of human-derived biological samples. Here, we report that micro-CT could be utilized to create virtual reconstructions of endoscopically obtained intestinal biopsies. The formed digital 3D images enabled selection of always optimal cutting angles for accurate measurement of the mucosal damage and revealed diagnostic lesions in cases interpreted as normal with conventional histomorphometry. We also demonstrate that computer-assisted point cloud analysis can be used to calculate biologically meaningful surface areas of the biopsies in different stages of mucosal damage with excellent replicability and correlation with other disease parameters. We expect the improved diagnostic accuracy and capability to measure the surface areas to provide a powerful tool for the diagnostics of intestinal diseases and for future clinical and pharmaceutical trials.

1180 Novel Capillary Catheter System Is Superior to Conventional Small Bowel Aspiration Catheter: An Important Development for Small Bowel Microbiome Assessment

INTRODUCTION: The small intestine is an understudied frontier of microbiome research. While aspiration during endoscopy is considered the gold standard to assess small bowel bacteria, the tools for sterile retrieval are primitive and poorly validated. Moreover, endoscopic aspiration is time consuming and prone to contamination. Inspired by plants’ ability to draw water via capillary action, a novel multi-capillary sterile system was designed. We examined the suctioning time and volume capabilities of this catheter using various liquids compared to conventional aspiration catheters. METHODS: Liquids with varying viscosities (water, 25% glucose solution and povidone iodine 10%) were used to assess the aspiration efficiency of the capillary catheter (MicroLotus, Hobbs Medical Inc.) ex-vivo as compared to a conventional small bowel aspiration catheter (Hobbs Medical Inc.) (Figure 1). Viscosity ranged between 0.89 mPa*s for water to 18 mPa*s for povidone. In the first experiment, 8 ml of each liquid was placed in a test tube. Catheters were completely submerged in the liquid and suction was applied using a standardized suctioning technique (Alliance™ II Integrated Inflation device). Next, the same four liquids were placed in a petri dish to mimic the flat mucosal surface. The technique was repeated with 3mL (typical volume of small bowel aspirate). Each experiment was repeated 10 times. RESULTS: The conventional catheter suffered from air entering the catheter when not completely submerged which is typical of the small bowel surface. In terms of speed of aspiration, the capillary catheter was at least 10 times faster than the conventional catheter for all fluid viscosities (Figure 2). Capillary catheter demonstrated increasing superiority with increasing viscosity (R = 0.96). When comparing aspiration on a flat surface, aspiration times were 4.67 + 1.35, 9.65 + 2.03 and 23.52 + 3.30 seconds for water, glucose and povidone for the capillary catheter, and too long to measure for the conventional due to concomitant superfluous air entry due to catheter design. CONCLUSION: The capillary aspiration catheter system is superior to conventional aspiration catheter in suctioning liquids with various viscosities. This new system may improve aspiration time and quality for small bowel aspiration. Overall, this new system could save between 1 and 6 minutes in endoscopy time to obtain aspirates depending upon the viscosity of the aspirating fluid. Future in-vivo studies are needed to further assess the capillary catheter.

Physiology of Energy Management

Physiology of Energy Management

Comparative analysis of rectal dose parameters in image-guided high-dose-rate brachytherapy for cervical cancer with and without a rectal retractor

The objective of this study was to determine if use of a rectal retractor (RR) in high-dose-rate intracavitary brachytherapy for cervical cancer reduces rectal dose parameters. We reviewed data obtained from patients treated with intracavitary brachytherapy for cervical cancer with and without an RR. Treatment plans for each brachytherapy fraction were separated into two groups; R group with use of an RR and P group with use of vaginal packing. Dose-volume parameters for high-risk clinical target volume (HR-CTV), rectum, sigmoid, small bowel, and vaginal surface were collected for each fraction. Rectal D2cc and International Commission on Radiation Units & Measurements (ICRU) rectal point doses were compared between groups using Student's t tests. Predictors of higher rectal D2cc were determined by univariate and multivariate regression analyses. Four hundred sixty-three brachytherapy fractions from 114 patients were used for analysis, 377 fractions with a RR (R group) and 86 with vaginal packing only (P group). Bothgroups were similar except for slightly higher mean HR-CTV and mean bladder volume in P group. Both mean ICRU rectal point dose (241.1 vs. 269.9cGy, p= 0.006) and rectal D2cc (240.6 vs. 283.6cGy, p < 0.001) were significantly higher in P group. Point A dose, HR-CTV, stage, and use of an RR were significant predictors of rectal D2cc on multivariate analysis. Our data show that use of an RR leads to lower rectal dose parameters compared with vaginal packing. Further study is needed to determine if this will lead to less long-term toxicity.

Galactosyl Human Serum Albumin-NMP1 Conjugate: A Near Infrared (NIR)-Activatable Fluorescence Imaging Agent to Detect Peritoneal Ovarian Cancer Metastases

Patient survival depends on the completeness of resection of peritoneal ovarian cancer metastases (POCM), and therefore, it is important to develop methods to enhance detection. Previous probe designs based on activatable galactosyl human serum albumin (hGSA)-fluorophore pairs, which target lectin receptors expressed on POCM, have used only visible range dyes conjugated to hGSA. However, imaging probes emitting fluorescence in the NIR range are advantageous because NIR photons have deeper in vivo tissue penetration and result in lower background autofluorescence than those emitting in the visible range. A NIR-activatable hGSA fluorophore was synthesized using a bacteriochlorin-based dye, NMP1. NMP1 has two unique absorption peaks, one in the green range and the other in the NIR range, but emits at a NIR peak of 780 nm. NMP1, thus, has two different Stokes shifts that have the potential to allow imaging of POCM both at the peritoneal surface and just below it. hGSA was conjugated with 2 NMP1 molecules to create a self-quenching complex (hGSA-NMP1). The activation ratio of hGSA-NMP1 was measured by the fluorescence intensity before and after exposure to 10% SDS. The activation ratio of hGSA-NMP1 was ~100-fold in vitro. Flow cytometry, fluorescence microscopy, and in vivo spectral fluorescence imaging were carried out to compare hGSA-NMP1 with hGSA-IR800 and hGSA-ICG (two always-on control agents with similar emission to NMP1) in terms of comparative fluorescence signal and the ability to detect POCM in mice models. The sensitivity and specificity of hGSA-NMP1 for POCM implant detection were determined by colocalizing NMP1 emission spectra with red fluorescent protein (RFP) expressed constitutively in SHIN3 tumor implants at different depths below the peritoneal surface. In vitro, SHIN3 cells were easily detectable after 3 h of incubation with hGSA-NMP1. In vivo submillimeter POCM foci were clearly detectable with spectral fluorescence imaging using hGSA-NMP1. Among 555 peritoneal lesions, hGSA-NMP, using NIR and green excitation light, respectively, detect 75% of all lesions and 91% of lesions ~0.8 mm or greater in diameter. Few false positives were encountered. Nodules located at a depth below the small bowel surface were only depicted with hGSA-NMP1. We conclude that hGSA-NMP1 is useful in imaging peritoneal ovarian cancer metastases, located both superficially and deep in the abdominal cavity.

Adherence of enteroaggregative Escherichia coli to the ileal and colonic mucosa: an in vitro study utilizing the scanning electron microscopy

Enteroaggregative Escherichia coli strains have been associated with persistent diarrhea in several developing countries. In vivo procedures with animal models, in vitro assays with cellular lines and in vitro organ culture with intestinal fragments have been utilized to study these bacteria and their pathogenicity. The present experimental research assessed the pathogenic interactions of three enteroaggregative Escherichia coli strains, using the in vitro organ culture, in order to show the adherence to different regions of both, the ileal and the colonic mucosa and demonstrate possible mechanisms that could have the participation in the prolongation of diarrheiogenic process. This study used intestinal fragments from terminal ileum and colon that were excised from pediatric patients undergoing intestinal surgeries and from adult patients that underwent to colonoscopic procedures. Each strain was tested with three intestinal fragments for each region. Tissue was fixed for scanning electron microscopic analysis. These bacteria colonized ileal and colonic mucosa in the typical stacked-brick configuration in the ileum and colon. In both regions, the strains were seen over a great amount of mucus and sometimes over the intact epithelium. In some regions, there is a probable evidence of effacement of the microvilli. It was possible to see adhered to the intestinal surface, bacteria fimbrial structures that could be responsible for the adherence process. In order to cause diarrhea, enteroaggregative Escherichia coli strains adhere to the intestinal mucosa, create a mucoid biofilm on the small bowel surface that could justify the digestive-absorptive abnormalities and consequently, prolonging the diarrhea.

Computed image modification for enhancement of small-bowel surface structures at video capsule endoscopy

Computed virtual chromoendoscopy with the Fujinon intelligent color-enhancement (FICE) system was reported to improve visualization of neoplastic and non-neoplastic lesions at gastroscopy and colonoscopy. The technique is based on narrowing the bandwidth of the conventional endoscopic image arithmetically by a spectral estimation technology. Implementation of the FICE software in the video capsule workstation might also allow for contrast-enhanced assessment of nature and extent of small-bowel mucosal lesions. Here we propose this novel technique and report on 10 consecutive patients who underwent small-bowel video capsule endoscopy that was evaluated with FICE-enhanced imaging.

Predictors of suboptimal surgical cytoreduction in women with advanced epithelial ovarian cancer treated with initial chemotherapy

The objective of this study was to retrospectively evaluate predictors of suboptimal surgical cytoreduction (SSC) in women with advanced epithelial ovarian cancer (EOC) treated with initial chemotherapy (IC). All women with EOC treated with IC at our hospital between January 1, 1995, and January 1, 2003, were eligible; 128 patients met inclusion criteria and underwent retrospective chart review. Eighty-four patients (66%) had an optimal surgical cytoreduction (OSC), 14 patients (11%) had an SSC, and 30 (23%) patients were treated with chemotherapy only (CO). Patients in the SSC group had more small-bowel mesentery disease on preoperative computed tomography (CT) scan compared to the OSC group (38% SSC vs 6% OSC,P= 0.024). Patients in the SSC group were also more likely to have disease on the liver surface, small-bowel surface, large-bowel mesentery, bladder peritoneum, spleen, and diaphragm that was not reported on preoperative CT but found at surgery. More patients in the SSC group had chemoresistant disease (indicated by stable or progressive disease on CT scan [56% SSC vs 17% OSC,P= 0.05]) and less of a decrease in their CA-125 values (69% SSC vs 93% OSC,P≤ 0.001) than patients in the OSC group. Many women with advanced EOC do not have OSC even if initially treated with IC. We created novel algorithms to identify patients who would likely have an SSC after IC. For those patients highly likely to have an SSC, CO may be offered as a reasonable alternative, decreasing the morbidity of an extensive surgical procedure that may not provide survival benefit.

Postoperative adverse events and long-term survival after cytoreductive surgery and intraperitoneal chemotherapy

Background Peritoneal carcinomatosis (PC) is fatal without special combined cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). This study was designed to identify factors that may increase the risk of postoperative morbidity and mortality from combined CRS and IPC interventions for PC. Survival based on primary tumour type and extent of surgery is reported. Methods Between May 1991 and November 2004, 123 patients were treated with CRS and IPC for PC. Based on the National Cancer Institute Common Toxicity Criteria for grade 3 and 4, data on 30 days postoperative morbidity and 90 days mortality were analysed. Results Grade 3–4 adverse events were observed in 51 patients (41%) and were associated with stoma formation, duration of surgery, peroperative blood loss and peritoneal cancer index (PCI). Excision, or electrocautery evaporation, of tumour from small bowel surface was correlated to bowel morbidity. Five patients had treatment-related mortality (4%) within 90 days. Survival was associated with macroscopic radical surgery, prior surgical score, PCI and primary tumour type. Conclusions CRS and IPC for PC are associated with high morbidity and mortality. However, in light of the potential benefit indicated by long-term survival, the adverse event from this treatment is considered acceptable.

Multiple Micronutrient Deficiencies in a Child With Short Bowel Syndrome and Normal Somatic Growth

Children with short bowel syndrome (SBS) are at risk for a variety of macro- and micronutrient deficiencies and other complications as a result of loss of small bowel surface area (1). The amount and location of small intestine loss in SBS will generally define the degree of nutrient malabsorption and the likelihood of micro-nutrient deficiencies. Duodenal resection, for example, can result in iron and folate deficiencies. Extensive jejunal resection can lead to malabsorption of carbohydrates, proteins, and calcium. The terminal ileum is the primary site of absorption of vitamin B12 and bile salts. Bile salt malabsorption can in turn present with steatorrhea and deficiencies of vitamins A, D, E, and K. Ileocolonic resection can predispose to several problems as a result of the loss of the ileocecal valve, resulting in loss of the ileal break, increased risk of anastomotic ulcers, and bacterial overgrowth. The extent of nutrient malabsorption in SBS is generally assessed by history and physical examination, including assessment of growth parameters. Normal somatic growth generally implies adequate energy and macronutrient absorption. We describe a patient with SBS who developed severe iron-deficiency anemia and multiple micronutrient deficiencies despite normal growth, full oral intake, and limited ileal resection.

Predictors of suboptimal surgical cytoreduction in women with advanced epithelial ovarian cancer treated with initial chemotherapy

The objective of this study was to retrospectively evaluate predictors of suboptimal surgical cytoreduction (SSC) in women with advanced epithelial ovarian cancer (EOC) treated with initial chemotherapy (IC). All women with EOC treated with IC at our hospital between January 1, 1995, and January 1, 2003, were eligible; 128 patients met inclusion criteria and underwent retrospective chart review. Eighty-four patients (66%) had an optimal surgical cytoreduction (OSC), 14 patients (11%) had an SSC, and 30 (23%) patients were treated with chemotherapy only (CO). Patients in the SSC group had more small-bowel mesentery disease on preoperative computed tomography (CT) scan compared to the OSC group (38% SSC vs 6% OSC, P = 0.024). Patients in the SSC group were also more likely to have disease on the liver surface, small-bowel surface, large-bowel mesentery, bladder peritoneum, spleen, and diaphragm that was not reported on preoperative CT but found at surgery. More patients in the SSC group had chemoresistant disease (indicated by stable or progressive disease on CT scan [56% SSC vs 17% OSC, P = 0.05]) and less of a decrease in their CA-125 values (69% SSC vs 93% OSC, P <or= 0.001) than patients in the OSC group. Many women with advanced EOC do not have OSC even if initially treated with IC. We created novel algorithms to identify patients who would likely have an SSC after IC. For those patients highly likely to have an SSC, CO may be offered as a reasonable alternative, decreasing the morbidity of an extensive surgical procedure that may not provide survival benefit.

Serum citrulline: a potential marker for intestinal epithelial mass and absorption capacity in short bowel syndrome patients

To investigate the potential role of serum citrulline level in evaluating the intestinal absorptive area and capacity in patients with short bowel syndrome (SBS). Serum citrulline concentration was determined using high performance liquid chromatography (HPLC) in SBS patients (n=22) and healthy controls (n=33). In SBS patients, the remnant small bowel lengths and diameters were measured by radiography, and their 5- hour urine D- xylose excretion and intestinal protein absorption were also determined. The correlationship of serum citrulline level with remnant small bowel length, surface area, protein and D- xylose absorption was analyzed. The 6 patients receiving intestinal rehabilitative therapy, serum citrulline level, protein and D- xylose absorption after therapy were also measured. Serum citrulline level of SBS patients was significantly lower than that of healthy controls [(5.94+/- 2.65) vs [(16.87 +/- 5.97) micromol/L, P < 0.01]. In SBS patients, serum citrulline was positively correlated with remnant small bowel length and surface area (r=0.82 and r=0.86 respectively). There was also a significant correlationship of serum citrulline level with 5- hour D- xylose excretion (r=0.56) and intestinal protein absorption (r=0.48). Serum citrulline, 5- hour D- xylose excretion and intestinal protein absorption were all significantly raised in patients after rehabilitative therapy, although no correlation of increasing percentage was found among above three parameters. Serum citrulline concentration is positively correlated with intestinal absorptive area and capacity in SBS patients. It is a potential marker for evaluating the severity of intestinal failure and the efficacy of rehabilitative therapy in short bowel patients.

Chronically administered retinoic acid has trophic effects in the rat small intestine and promotes adaptation in a resection model of short bowel syndrome

Following the loss of functional small bowel surface area, the intestine undergoes a compensatory adaptive response. The observation that adaptation is inhibited in vitamin A-deficient rats following submassive intestinal resection suggested that vitamin A is required for this response and raised the possibility that exogenous vitamin A could augment adaptation. Therefore, to directly assess whether chronically administered retinoic acid could stimulate gut adaptation in a model of short bowel syndrome and to address the mechanisms of any such effects, Sprague-Dawley rats were implanted with controlled release retinoic acid or control pellets and then subjected to mid-small bowel or sham resections. At 2 wk postoperation, changes in gut morphology, crypt cell proliferation and apoptosis, enterocyte migration, the extracellular matrix, and gene expression were assessed. Retinoic acid had significant trophic effects in resected and sham-resected rats. Retinoic acid markedly inhibited apoptosis and stimulated crypt cell proliferation and enterocyte migration postresection. Data presented indicate that these proadaptive effects of retinoic acid may be mediated via changes in the extracellular matrix (e.g., by increasing collagen IV synthesis, decreasing E-cadherin expression, and reducing integrin beta(3) levels), via affects on Hedgehog signaling (e.g., by reducing expression of the Hedgehog receptors Ptch and Ptch2 and the Gli1 transcription factor), by increasing expression of Reg1 and Pap1, and by modulation of retinoid and peroxisome proliferator-activated receptor signaling pathways. These studies are the first to demonstrate that retinoic acid can significantly enhance intestinal adaptation and suggest it may be beneficial in patients with short bowel syndrome.

Increased apoptosis and accelerated epithelial migration following inhibition of hedgehog signaling in adaptive small bowel postresection

The intestinal epithelium undergoes a marked adaptive response following loss of functional small bowel surface area characterized by increased crypt cell proliferation and increased enterocyte migration from crypt to villus tip, resulting in villus hyperplasia and enhanced nutrient absorption. Hedgehog (Hh) signaling plays a critical role in regulating epithelial-mesenchymal interactions during morphogenesis of the embryonic intestine. Our previous studies showed that blocking Hh signaling in neonatal mice results in increased small intestinal epithelial crypt cell proliferation and altered enterocyte fat absorption and morphology. Hh family members are also expressed in the adult intestine, but their role in the mature small bowel is unclear. With the use of a model of intestinal adaptation following partial small bowel resection, the role of Hh signaling in the adult gut was examined by determining the effects of blocking Hh signaling on the regenerative response following loss of functional surface area. Hh-inactivating monoclonal antibodies or control antibodies were administered to mice that sustained a 50% intestinal resection. mRNA analyses of the preoperative ileum by quantitative real-time PCR revealed that Indian hedgehog was the most abundant Hh family member. The Hh receptor Patched was more abundant than Patched 2. Analyses of downstream targets of Hh signaling demonstrated that Gli3 was twofold more abundant than Gli1 and Gli2 and that bone morphogenetic protein (BMP)2 was most highly expressed compared with BMP1, -4, and -7. Following intestinal resection, the expression of Hh, Patched, Gli, and most BMP genes was markedly downregulated in the remnant ileum, and, in anti-Hh antibody-treated mice, expression of Patched 2 and Gli 1 was further suppressed. In Hh antibody-treated mice following resection, the enterocyte migration rate from crypt to villus tip was increased, and by 2 wk postoperation, apoptosis was increased in the adaptive gut. However, crypt cell proliferation, villus height, and crypt depth were not augmented. These data indicate that Hh signaling plays a role in adult gut epithelial homeostasis by regulating epithelial cell migration from crypt to villus tip and by enhancing apoptosis.

Arguments for a lower carbohydrate-higher fat diet in patients with a short small bowel

Short small bowel patients suffer from malabsorption due to a strongly reduced small bowel surface. These patients usually get a high caloric high carbohydrate-low fat diet at oral or enteral feeding. At several points our studies demonstrate that the effect of this formula is doubtful. In these patients the intestinal flora has strongly been changed and even become characteristic due to abundant presence of lactobacilli (up to nearly 100%). In many patients with a high carbohydrate-low fat diet these bacteria both produce massive amounts of d-lactic acid and gaseous CO2, and they destroy the primary bile acids that are necessary for uptake of lipids. Thus, they cause (i) an increased risk of D-lactic acidosis and D-lactic acid-associated encephalopathy, (ii) flatulence, abdominal pain and non-infectious diarrhoea, and (iii) low uptake of fat and lipophilic vitamins. It is argued that by gradually converting the diet to a low carbohydrate-high fat diet growth of the characteristic lactobacilli can be strongly reduced and so also the mentioned inconveniences.

Targeted Intestinal Overexpression of the Immediate Early Gene tis7 in Transgenic Mice Increases Triglyceride Absorption and Adiposity

Following loss of functional small bowel surface area due to surgical resection, the remnant gut undergoes an adaptive response characterized by increased crypt cell proliferation and enhanced villus height and crypt depth, resulting in augmented intestinal nutrient absorptive capacity. Previous studies showed that expression of the immediate early gene tis7 is markedly up-regulated in intestinal enterocytes during the adaptive response. To study its role in the enterocyte, transgenic mice were generated that specifically overexpress TIS7 in the gut. Nucleotides -596 to +21 of the rat liver fatty acid-binding protein promoter were used to direct abundant overexpression of TIS7 into small intestinal upper crypt and villus enterocytes. TIS7 transgenic mice had increased total body adiposity and decreased lean muscle mass compared with normal littermates. Oxygen consumption levels, body weight, surface area, and small bowel weight were decreased. On a high fat diet, transgenic mice exhibited a more rapid and proportionately greater gain in body weight with persistently elevated total body adiposity and increased hepatic fat accumulation. Bolus fat feeding resulted in a greater increase in serum triglyceride levels and an accelerated appearance of enterocytic, lamina propria, and hepatic fat. Changes in fat homeostasis were linked to increased expression of genes involved in enterocytic triglyceride metabolism and changes in growth with decreased insulin-like growth factor-1 expression. Thus, TIS7 overexpression in the intestine altered growth, metabolic rate, adiposity, and intestinal triglyceride absorption. These results suggest that TIS7 is a unique mediator of nutrient absorptive and metabolic adaptation following gut resection.

Serum Citrulline Is A Simple Quantitative Marker for Small Intestinal Enterocytes Mass and Absorption Function in Short Bowel Patients

To investigate the clinical significance of serum citrulline in evaluating the remnant small bowel enterocytes mass and absorptive function in short bowel (SB) patients. Serum citrulline concentrations were determined using high-performance liquid chromatography (HPLC) in 22 SBS patients and 33 healthy controls. Five-hour urine D-xylose excretion and digestive protein absorption were measured using HPLC and micro-Kjeldahl method, respectively. Small bowel length and surface area were assessed on X-ray radiograph. Correlations between serum citrulline levels and small bowel length, small bowel surface, and nutritional substrate digestive absorption percentage were analyzed. For six patients receiving bowel rehabilitation therapy, serum citrulline, D-xylose excretion, and intestinal protein absorption were measured pre- and immediately postmanagement, and their correlations were analyzed. Serum citrulline levels were significantly lower in SB patients compared with healthy controls. In SB patients, they correlated well with remnant small bowel length (r = 0.82, P < 0.001), surface area (r = 0.86, P < 0.001), 5-h urine D-xylose excretion (r = 0.56, P = 0.007), and digestive protein absorption (r = 0.48, P = 0.046). The increased percentage of serum citrulline level in six patients receiving rehabilitation therapy followed a trend of correlating with that of intestinal protein absorption (r = 0.79, P = 0.063) and urine D-xylose excretion (r = 0.81, P = 0.053). In patients with short bowel syndrome, serum citrulline is a simple and accurate biomarker for the severity of intestinal failure and may be a candidate marker for the gut-trophic effects of bowel rehabilitation therapies.

Late Regeneration of Infarcted Small Bowel Mucosa: A Case Report

Ischemic injury of the small bowel may recover after revascularization, provided that full-thickness infarction did not occur. Animal studies showed that if the mucosal crypts remain viable, rapid mucosal restitution occurs hours after injury. The treatment of transmucosal infarction that does not extend to full wall thickness, however, was not investigated thoroughly. The patient presented had a mesenteric event leading to resection of about half of his small bowel. The unresected segment had severe ischemic injury, which seemed to cause transmucosal, but not transmural, infarction. Imaging of the remaining small bowel revealed a seromuscular layer denuded of mucosa. The ischemic damage was too deep to allow rapid regeneration, and the patient had short-bowel syndrome. A year later, during operation for stricture complications, new mucosa covered parts of the small-bowel surface, encouraging the surgeon to elect a conservative approach. Sixteen months after the injury, normal mucosa covered the entire small bowel, and enteral feeding resumed successfully. This report shows that infarcted small-bowel mucosa may regenerate even months after injury.