Amy E. Foxx-Orenstein

Percutaneous endoscopic gastrojejunostomy: a dual center safety and efficacy trial.

Although jejunal tube placement through a percutaneous endoscopic gastrostomy (PEG) has not been proven to be preferable to PEG feeding, it would be theoretically advantageous for those patients prone to gastrointestinal aspiration. However, reliable placement of a small bowel feeding tube through a PEG has been technically difficult. We have previously reported successful placement of a percutaneous endoscopic gastrojejunostomy (PEG/J) with minimal complications. These results are in contrast to other series that report technical difficulty, frequent tube dysfunction and gastric aspiration. We describe an over-the-wire PEG/J technique performed by multiple operators at two medical centers. Gastrostomy tube placement was successful in 94% of patients. Initial placement of the jejunal tube was successful in 88% of patients. Second attempts were 100% successful. The average procedure time was 36 minutes. The distal duodenal and jejunal placement of the jejunal tube resulted in no episodes of gastroduodenal reflux. Complications included jejunal tube migration (6%), clogging (18%), and unintentional removal (11%). The majority of patients were ultimately converted to either oral or intragastric feedings. We conclude that the PEG/J system is a reliable, reproducible method of small bowel feeding and is associated with no episodes of tube feeding reflux when the jejunal tube is positioned in the distal duodenum or beyond. Furthermore, it provides a temporary nutritional bridge for those patients who are later transitioned to either PEG or oral feeding.

The Microenvironment of Human Peyer’s Patches Inhibits the Increase in CD38 Expression Associated with the Germinal Center Reaction

Analysis of B cells in the human tonsils identified CD38 expression as a hallmark of germinal center (GC) B cells. However, the signals responsible for the in vivo induction of CD38 have not been determined. The primary site for generation of memory and plasma cells in the gastrointestinal tract is the GCs of Peyer’s patches (PP). PP and intestinal mucosa, but not tonsils or oral mucosa, express mucosal addressin cell adhesion molecule-1 (MAdCAM-1). The ligand for MAdCAM-1, integrin α4β7, is expressed on naive B cells and memory B cells that traffic to the gastrointestinal tract. In this study we determine that, unlike tonsil, human PP GC B cells do not express significant levels of CD38. PP B cells can be induced to express CD38 upon culture with CD40 ligand, anti-B cell receptor, and IFN-γ. However, coculture of tonsil naive B cells with an Ab directed against integrin β7 inhibits IFN-γ-induced CD38 hyperexpression. The absence of CD38 on PP GCs suggests that there are tissue-specific pathways of B cell development that differ between tonsil and PP. The differential expression pattern of MAdCAM-1, together with the observation that ligation of β7 can inhibit the induction of CD38 expression, suggests that ligation of α4β7 in vivo may contribute to a PP-specific GC phenotype.

The Impact of Pelvic Floor and Lower Gastrointestinal Symptoms on Quality of Life in Women With Systemic Sclerosis.

Background: Systemic sclerosis (SSc) patients with gastrointestinal (GI) involvement have a lower quality of life (QoL) and while the impact of upper GI symptoms on QoL in SSc patients has been described few data exist on the presence and impact of lower gastrointestinal (LGI) and pelvic floor symptoms in SSc. Our goal was to assess the prevalence of these symptoms in women with SSc and evaluate their impact on QoL. A secondary hypothesis was that the impact of LGI symptoms on QoL is mediated by depression. Study: Women with SSc (n=175) attending an outpatient scleroderma clinic completed multiple validated questionnaires. Pelvic floor and LGI symptoms included fecal incontinence (FI), urinary incontinence (UI), dual incontinence (DI), chronic constipation, diarrhea, and pelvic pain. The Student t tests adjusted for multiple comparisons were used to evaluate group differences at the 0.05 level. Results: Complete data were available for 160 women. FI was reported by 65, UI by 64, DI by 40, chronic constipation by 94, diarrhea by 82, and pelvic pain by 35 of SSc patients. Overall QoL was reduced in SSc patients with FI (0.96 vs. 0.63; P=0.007), UI (0.96 vs. 0.65; P=0.01), DI (1.11 vs. 0.67; P=0.002), and pelvic pain (1.01 vs. 0.70; P=0.04). Antidepressant use was reported by 26%. The negative impact on QoL in patients with pelvic floor symptoms was partially mediated by depression. Conclusions: Women with SSc suffer from an increased prevalence of LGI and pelvic floor symptoms including FI, UI, diarrhea, constipation, and pelvic pain and this effect seems to be partially mediated by depression.

Sa2043 The Impact of Lower Gastrointestinal Symptoms on Quality of Life in Women With Systemic Sclerosis

G A A b st ra ct s assessed by surface electromyography (EMG). Results: A total of 36 women with FI were randomized to HES or SBT (18 in each treatment group). Groups were matched by mean age: 65.5±13.5 years, mean BMI (kg/m2): 26.2±3.9, mean disease duration: 1.42±0.8 yrs, mean number of births: 2.7±1.3 and reports of obstetric trauma (25%). Only patients that received HES reported a significant improvement of FIGS (p=0.0015) and a significant drop in the number of leaked solid and liquid stool (p=0.012, p= 0.07, respectively). SF-36 scores were not affected significantly by treatment in both groups. A significant improvement of PEM contraction was achieved in 89 % of patients from both groups. Conclusions: Home electric stimulation only was found to be more efficient than standardized biofeedback training only if assessed by both subjective and objective measures.

Assessment of human colon cancer protein kinetics in vivo

BACKGROUND Malignancies enlarge because protein synthesis exceeds the rate of breakdown; however, the specific protein kinetic pattern remains unknown. Determining in vivo protein kinetic rates for a tumor may be useful for quantifying individual responses to a specific therapy. The aim of this study was to assess whether the growth of tumors is related to an increase in protein synthesis or an inhibition of protein breakdown. METHODS Five patients (age, 59 +/- 3 years) with adenocarcinoma of the colon undergoing colonoscopy were studied. Tissue protein synthesis and breakdown rates were measured in vivo for both segments of colon cancer and adjacent normal-appearing colonic mucosa by using a primed, continuous infusion of 1(13)C leucine with tissue biopsy and quantitation of regional blood flow by laser Doppler flowmetry. RESULTS Segments of colon cancer had a significantly (p < 0.05) greater rate of protein synthesis as quantitated by both the fractional rate of protein synthesis (Ca 45.4% +/- 5.0%/day versus nl mucosa 35.7% +/- 3.1%/day; mean +/- SEM) and by the tissue synthesis rate (Ca 69.4 +/- 9.0 versus nl mucosa 51.6 +/- 5.2 mumol/L leucine/day/100 gm tissue). Regional blood flow was significantly elevated in the cancer (Ca 110.9 +/- 5.8 versus nl mucosa 91.2 +/- 2.9 ml/min/100 gm), which contributed to commensurate rates of tissue breakdown (Ca 28.6 +/- 2.0 versus nl mucosa 28.2 +/- 2.4 mumol/L leucine/day/100 gm). CONCLUSIONS These results illustrate that human colon cancers grow in vivo as a result of increases in protein synthesis. Furthermore, increases in regional blood flow limit the rate of tissue protein breakdown of colon cancer, thereby contributing to growth of the malignancy. These findings support the contention that therapeutic strategies aimed at negating this inherent increase in protein synthesis or limiting blood flow may effectively limit the growth of malignancies. This methodology may also provide an index for evaluating the effectiveness of future therapies aimed at reducing tumor growth for individual patients.