Macronutrient absorption characteristics in humans with short bowel syndrome and jejunocolonic anastomosis: starch is the most important carbohydrate substrate, although pectin supplementation may modestly enhance short chain fatty acid production and fluid absorption.

BACKGROUND: Diet may play an important role in the management of patients with short bowel syndrome who have colon in continuity. However, macronutrient absorption has not been well characterized, and the most appropriate dietary constituents have not been well defined. OBJECTIVE: To define carbohydrate absorption characteristics in patients with short bowel syndrome and determine the potential role of pectin as a dietary substrate. METHODS: The authors studied the effect of a custom pectin-based supplement in 6 subjects (3 male/3 female) aged 29-67 years with jejunocolonic anastomosis, 4 of whom required long-term parental nutrition. Small intestinal absorption capacity, macronutrient and fluid balance, gastrointestinal transit time, and energy consumption were measured. RESULTS: Data showed that 53% nitrogen, 50% fat, and 32% total energy were malabsorbed. In contrast, the majority (92%) of total carbohydrate was utilized. Fecal short-chain fatty acids (SCFAs) were increased, an indication of increased fermentation. Although only 4% of starch was recovered in stool, it is indicative of considerable starch malabsorption, thus providing the main carbohydrate substrate, for colonic bacterial fermentation. In contrast, nonstarch polysaccharide was a relatively minor fermentation substrate with only 49% utilized. Eighty percent of the pectin was fermented. Supplementation was associated with increased total SCFAs, acetate, and propionate excretion. There was a trend observed toward greater fluid absorption (-5.9% ± 54.4% to 26.9% ± 25.2%) following pectin supplementation. Nonsignificant increases in gastric emptying time and orocolonic transit time were observed. CONCLUSION: Despite malabsorption, starch is the primary carbohydrate substrate for colonic bacterial fermentation in patients with short bowel syndrome, although soluble fiber intake also enhances colonic SCFA production.

The novel expanded porphyrin, motexafin gadolinium, combined with [90Y]ibritumomab tiuxetan for relapsed/refractory non-Hodgkin's lymphoma: preclinical findings and results of a phase I trial.

PURPOSE: Therapeutic strategies to enhance the efficacy of radioimmunotherapy have not been explored. Motexafin gadolinium is a novel anticancer agent that targets redox-dependent pathways and enhances sensitivity of tumor cells to ionizing radiation. EXPERIMENTAL DESIGN: We did preclinical studies examining motexafin gadolinium combined with rituximab and/or radiation in lymphoma cells. We subsequently completed a phase I clinical trial combining escalating doses of motexafin gadolinium concurrently with standard [(90)Y]ibritumomab tiuxetan for patients with relapsed/refractory non-Hodgkin's lymphoma. RESULTS: In HF1 lymphoma cells, motexafin gadolinium and rituximab resulted in synergistic cytotoxicity (combination index, 0.757) through a mitochondrial-mediated caspase-dependent pathway, whereas cell death in Ramos and SUDHL4 cells was additive. Motexafin gadolinium/rituximab combined with radiation (1-3 Gy) resulted in additive apoptosis. Twenty-eight of 30 patients were evaluable on the phase I clinical trial. Median age was 65 years (47-87 years), and histologies were marginal-zone (n = 1), mantle-cell (n = 3), diffuse large cell (n = 6), and follicular lymphoma (n = 18). Of all patients, 86% were rituximab refractory. Therapy was well tolerated, and no dose-limiting toxicity was seen. Overall response rate was 57% [complete remission (CR), 43%], with median time-to-treatment failure of 10 months (1-48+ months) and median duration-of-response of 17 months. Of note, all responses were documented at 4 weeks. Furthermore, in rituximab-refractory follicular lymphoma (n = 14), overall response rate was 86% (CR, 64%), with a median time-to-treatment failure of 14 months (2-48+ months). CONCLUSIONS: This represents the first report of a novel agent to be combined safely concurrently with radioimmunotherapy. Furthermore, tumor responses with [(90)Y]ibritumomab tiuxetan/motexafin gadolinium were prompt with a high rate of CRs, especially in rituximab-refractory follicular lymphoma.