Hossam M. Kandil

Cyclooxygenase-2 Expression in Barrett's Esophagus

Barretts epithelium is a recognized premalignant condition for esophageal adenocarcinoma. Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the relative risk of colon cancer in humans and the esophageal tumor load in carcinogen-treated mice. Previous studies provided conflicting results for COX-2 activity in Barretts mucosa. Pinch mucosal biopsies were collected from Barretts and adjacent normal esophageal mucosa from 17 patients with Barretts esophagus. Low-grade dysplasia was found in seven patients. COX-2 protein was undetectable in normal esophageal mucosa. COX-1 protein expression did not vary between normal and Barretts epithelium. Increased COX-2 protein was detected in Barretts epithelium in seven patients (41%) but did not differ with or without dysplasia (43% vs 40%). In conclusion, COX-2 protein is increased in 41% of patients with Barretts epithelium compared to normal esophageal mucosa but did not differ with or without dysplasia. COX-2 induction may be an early event in the development of Barretts esophagus.

Nutrition and Quality of Life Following Small Intestinal Transplantation

BACKGROUND:The outcome from small bowel transplantation (SBTx) has improved progressively over the past decade raising questions as to whether indications should be broadened from those currently followed based on “TPN (total parenteral nutrition) failure.”OBJECTIVE AND METHODS:To assess current outcome, we studied the effect of transplantation on nutritional autonomy, organ function, and quality of life (QoL) measured by a validated self-administered questionnaire containing 26 domains and 130 questions, for a minimum of 12 months in a cohort of 46 consecutively transplanted patients between June 2003 and July 2004. The majority of transplanted patients (76%) had intestinal failure because of extreme short bowel, the remainder having either chronic pseudo-obstruction or porto-mesenteric vein thrombosis (PMVT). All but the PMVT patients were dependent on home TPN (HPN) (median 2, range 0–25 yr) and had developed serious recurrent infective complications with (25%) or without central vein thrombosis and liver failure. Sixty-one percent received a liver in addition to a small intestine.RESULTS:Follow-up was for a mean of 21 (range 12–36) months. Five patients died, two with chronic graft rejection. All the remaining patients have graft survival with an average of 1.2 (range 0–5) episodes of acute rejection. All patients were weaned from TPN by a median of 18 days (range 1–117 days) and from tube feeding by day 69 (range 22–272 days). There was a significant improvement in overall assessment of QoL and in 13 of 26 of the specific domains examined.CONCLUSION:Our results confirm the claim that a new era has dawned for SBTx, such that, with continued progress, it can potentially become an alternative to HPN for the management of permanent intestinal failure, rather than a last-chance treatment for “TPN failure.”

Short Bowel Syndrome: Clinical Guidelines for Nutrition Management

Intestinal failure is a condition in which inadequate digestion or absorption of fluid, electrolytes, and nutrients leads to dehydration or malnutrition. The most common cause of intestinal failure is short bowel syndrome (SBS) defined as <200 cm of functional small intestine. SBS may result from congenital abnormalities or from surgical resection. For the past 3 decades, patients with severe SBS were managed with home parenteral nutrition (HPN). With the emergence of new therapies, the clinician now has multiple options to treat these patients. These include intestinal rehabilitation regimens whereby patients are treated with specialized oral diets, soluble fiber, oral rehydration solutions (ORS), and trophic factors to enhance absorption. There are also a variety of surgical techniques available to preserve intestinal length. Small bowel and multivisceral transplantation has evolved during the last decade to be a valid therapeutic option for those patients who cannot be rehabilitated or who fail HPN. These are interrelated services designed to offer the patient the best therapeutic options to meet their individual needs. This article reviews the principles associated with the nutrition management of this very complex and diverse group of patients.

Celecoxib and rofecoxib potentiate chronic colitis and premalignant changes in interleukin 10 knockout mice

Nonsteroidal anti-inflammatory drugs decrease sporadic colorectal carcinoma and adenomas in patients with familial adenomatous polyposis and in rodent models of sporadic colon cancer and familial adenomatous polyposis. Similarly, selective cyclooxygenase 2 inhibitors decrease adenomas in humans and rodents. However, their effects on chronic colitis and colitis-associated neoplasia are unknown. Interleukin 10−/− mice (C57/B6) were fed regular chow (n = 20) or chow with celecoxib (1,500 ppm, n = 18) or rofecoxib (75 ppm, n = 20) for 12 weeks. Twenty-eight percent of the celecoxib group died versus 5% of the control and rofecoxib groups (p < 0.05 compared with control). Celecoxib and rofecoxib increased the incidence of colitis (26% vs. 92% and 68%, p < 0.01), colitis score (0.4 ± 0.2 vs. 2.5 ± 0.3 and 2 ± 0.4, p < 0.01), aberrant crypt foci (0.5 ± 0.3 vs. 3.7 ± 2.6 and 2.8 ± 0.7, p < 0.01), aberrant crypts per mouse (4.11 ± 2.1 vs. 41.2 ± 9.7 and 27.1 ± 7.5, p < 0.01) and dysplasia (11% vs. 54% and 42%, p < 0.01). Similarly, indomethacin (9 ppm, n = 15) increased colitis score, aberrant crypt foci, and dysplasia after 27 days of treatment. Two selective cyclooxygenase 2 inhibitors exacerbate colitis and premalignant changes in the interleukin 10−/− mouse model of chronic colitis and colitis-associated colon carcinoma.

Early Jejunal Feeding Initiation and Clinical Outcomes in Patients with Severe Acute Pancreatitis

BACKGROUND Compared with parenteral nutrition, enteral nutrition reduces infectious complications and mortality in patients with severe acute pancreatitis (SAP). This study used clinical outcomes to investigate the association between time to initiation of distal jejunal feeding (DJF) and time to achievement of goal enteral feeding with clinical outcomes. METHODS A retrospective chart review was performed on all patients with SAP admitted to the medical intensive care unit (ICU) during a 1-year period. Collected data included demographic information, body mass index (BMI; kg/m(2)), Acute Physiology and Chronic Health Evaluation (APACHE) II scores at admission, time of onset of DJF, time to goal feeding, ICU length of stay, and mortality. RESULTS Time to starting DJF was longer in nonsurvivors (n = 4) than in survivors (n = 12) (17 vs 7 days, P < .05). All nonsurvivors had BMI >30 kg/m(2) (50% had BMI > 50 kg/m(2)). ICU length of stay was significantly associated with achievement of goal feeding. Three patients never reached goal feeding and spent 45.3 ± 19.6 days in the ICU; 7 patients reached goal feeding within 3 days of initiating DJF and spent 18 ± 1.7 days in the ICU; and 4 patients reached goal feeding within 3 days and spent 10.5 ± 3.5 days in the ICU. APACHE II scores were not significantly different among the 3 groups (16.7 ± 1.5, 12 ± 0.7, and 16.2 ± 1.2, respectively, P > .05). CONCLUSIONS Early initiation of DJF in the ICU was associated with reduced mortality in this cohort of patients with SAP. Early achievement of jejunal feeding goal early was associated with a shorter ICU length of stay, irrespective of the severity of SAP.

Nutritional factors in inflammatory bowel disease.

Dietary antigens may act as important stimuli of the mucosal immune system and have led to the study of nutritional therapy for IBD. Patients with active CD respond to bowel rest, along with total enteral nutrition or TPN. Bowel rest and TPN are as effective as corticosteroids at inducing remission for patients with active CD, although benefits are short-lived. Enteral nutrition is consistently less effective than conventional corticosteroids for treatment of active CD. Use of palatable, liquid polymeric diets in active CD is controversial, but these diets are of equal efficacy when compared with elemental diets. UC has not been treated effectively with either elemental diets or TPN. Fish oil contains n-3-PUFA, which inhibits production of proinflammatory cytokines and has some benefit in the treatment of CD. Topical applications of short-chain fatty acids have benefited diversion colitis and distal UC, whereas probiotics hold promise in the treatment of pouchitis.

Factors Predicting Recurrence of Clostridium difficile Infection (CDI) in Hospitalized Patients: Retrospective Study of More Than 2000 Patients

Background Clostridium difficile infection (CDI) has increased in incidence and severity worldwide, causing direct costs estimated to range from US

Gut rehabilitation and intestinal transplantation

3.2 billion to

Low vitamin D level and impact on severity and recurrence of Clostridium difficile infections.

4.8 billion. The aim of this study was to investigate and identify factors that predict recurrence of CDI. Methods This was a retrospective case-control study between 2007 and 2013 on patients admitted with CDI. Recurrent CDI is defined as a new episode of diarrhea within 90 days confirmed by a positive stool C. difficile toxin assay or polymerase chain reaction, after resolution of the initial CDI episode for at least 10 days and after discontinuation of the CDI therapy. Results Three thousand twenty patients were diagnosed with CDI between January 2007 and December 2013. Two hundred nine of 2019 patients in the study had a recurrence of CDI within 90 days of the end of the initial CDI episode (10.3%). Multivariate analysis showed that most of the recurrences occurred in patients with comorbidities, particularly chronic kidney disease (odds ratio, 1.3; 95% confidence interval [CI], 1.0–2.4; P = 0.039). In addition, a higher percentage of patients in the recurrence group were prescribed proton-pump inhibitors (odds ratio, 1.65; 95% CI, 1.0–1.7; P = 0.002) and steroids (odds ratio, 1.65; 95% CI, 1.0–1.5; P = 0.047). Conclusions Our data suggest that the use of glucocorticoids, use of proton-pump inhibitors, and having end-stage renal disease are significant risk factors associated with recurrent CDI.

Primary duodenal carcinoma showing divergent growth patterns as determined by microdissection-based mutational genotyping

The field of short bowel syndrome and gastrointestinal failure has recently evolved, particularly after the clinical introduction of intestinal and multivisceral transplantation. For nearly three decades, the management of short bowel syndrome was limited to the natural adaptation process and lifelong intravenous supplementation. However, recent clinical availability of intestinal transplantation as an alternative to total parenteral nutrition, has fueled the field with relentless efforts to enhance intestinal adaptation and gut rehabilitation with the achievement of full nutritional autonomy. Intestinal and multivisceral transplantation has added new dimensions as a creative therapy to short bowel syndrome patients, as well as those with extensive abdominal pathology that could not be treated with conventional methods. With continuous improvement in the survival outcome, the procedure has become more widely applicable and commonly utilized, with more than 65 intestinal transplant centers worldwide. With the procedure currently showing improvement in therapeutic indices, including cost effectiveness and quality of life, we believe intestinal and multivisceral transplantation should promptly be offered to short bowel syndrome patients who fail conventional rehabilitation as well as those with complex abdominal pathology.