Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) treatment enhance intestinal adaptation. To determine whether these growth factors exert synergistic effects on intestinal growth and function, GLP-2 and EGF-containing media (EGF-cm) were administered, alone and in combination, in neonatal piglet models of short bowel syndrome (SBS). Neonatal Landrace-Large White piglets were block randomized to 75% midintestinal [jejunoileal (JI) group] or distal intestinal [jejunocolic (JC) group] resection or sham control, with 7-day infusion of saline (control), intravenous human GLP-2 (11 nmol·kg⁻¹·day⁻¹) alone, enteral EGF-cm (80 μg·kg⁻¹·day⁻¹) alone, or GLP-2 and EGF-cm in combination. Adaptation was assessed by intestinal length, histopathology, Üssing chamber analysis, and real-time quantitative PCR of intestinal growth factors. Combined EGF-cm and GLP-2 treatment increased intestinal length in all three surgical models ( P < 0.01). EGF-cm alone selectively increased bowel weight per length and jejunal villus height in the JI group only. The JC group demonstrated increased intestinal weight and villus height ( P < 0.01) when given either GLP-2 alone or in combination with EGF-cm, with no effect of EGF-cm alone. Jejunal permeability of mannitol and polyethylene glycol decreased with combination therapy in both SBS groups ( P < 0.05). No difference was observed in fat absorption or body weight gain. IGF-1 mRNA was differentially expressed in JI vs. JC piglets with treatment. Combined treatment with GLP-2 and EGF-cm induced intestinal lengthening and decreased permeability, in addition to the trophic effects of GLP-2 alone. Our findings demonstrate the benefits of novel combination GLP-2 and EGF treatment for neonatal SBS, especially in the JC model representing most human infants with SBS. NEW & NOTEWORTHY Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) are intestinotrophic, with demonstrated benefit in both animal models and human studies of short bowel syndrome (SBS). The current research shows that over and above known trophic effects, the combination of GLP-2 and EGF synergistically lengthens the bowel in neonatal piglet models of SBS. Most notable benefit occurred with resection of the terminal ileum, the common clinical anatomy seen in neonatal SBS and associated with least de novo lengthening postsurgery.

PURPOSE: The affect of race on breast cancer prognosis is not well understood. We compared crude and adjusted breast cancer survival rates of Chinese women versus White women in the United States. METHODS: We conducted a cohort study of Chinese and White women with breast cancer diagnosed between 2004 to 2015 in the SEER 18 registries database. We abstracted information on age at diagnosis, tumor size, grade, lymph node status, receptor status, surgical treatment, receipt of radiotherapy and chemotherapy, and death. We compared crude breast cancer–specific mortality between the two ethnic groups. We calculated adjusted hazard ratios (HRs) in a propensity-matched design using the Cox proportional hazards model. P < .05 was considered statistically significant. RESULTS: There were 7,553 Chinese women (1.8%) and 414,618 White women (98.2%) with stage I-IV breast cancer in the SEER database. There were small differences in demographics, nodal burden, and clinical stage between Chinese and White women. Ten-year breast cancer–specific survival was 88.8% for Chinese women and 85.6% for White women (HR, 0.73; 95% CI, 0.67 to 0.80; P < .0001). In a propensity-matched analysis among women with stage I–IIIC breast cancer, the HR was 0.71 (95% CI, 0.62 to 0.81; P < .0001). Annual mortality rates in White women exceeded those in Chinese women for the first 9 years after diagnosis. CONCLUSION: Chinese women in the United States have superior breast cancer–specific survival compared with White women. The reason for the observed difference is not clear. Differences in demographic and tumor features between Chinese and White women with breast cancer may contribute to the disparity, as may the possibility of intrinsic biologic differences.

Background: Many women with early-stage breast cancer are predicted to be at sufficiently low risk for recurrence that they may forego chemotherapy. Nevertheless, some low-risk women will experience a local recurrence, and for them the risk of death increases significantly thereafter. The utility of initiating chemotherapy at the time of local recurrence has not been adequately addressed. The purpose of this study is to identify, in a hospital-based series of patients with early-stage breast cancer who were not treated with chemotherapy, those factors which predict death post local recurrence. Methods: We identified 135 women who were diagnosed with early-stage breast cancer (node-negative, <5 cm) and who did not receive chemotherapy at diagnosis and who developed a local recurrence. They were diagnosed between 1987 and 2000 and treated at Women’s College Hospital. For each patient, we abstracted information on the initial cancer (age at diagnosis, tumour size, tumour grade, ER status, PR status, HER2 status, lympho-vascular invasion, type of surgery, use of radiotherapy, tamoxifen and chemotherapy), the time from initial diagnosis to local recurrence and treatment at recurrence. The Kaplan–Meier method was used to estimate the ten-year actuarial risk of breast cancer death post recurrence. A Cox proportional hazards model was used to estimate multivariate hazard ratios for the various factors. Results: Among the 135 women in the cohort, the mean time from initial diagnosis to local recurrence was 7.8 years (range: 0.3 to 22.6 years). A total of 38 of the 135 women (28.1%) died of breast cancer a mean of 5.3 years after experiencing the local recurrence (range: 0.3 to 17 years). The ten-year breast cancer survival post local recurrence was 71% and the 15-year survival was 65%. In a multivariate analysis, it was found that factors that were significantly associated with death after local recurrence were (1) PR-negative status, (2) young age at diagnosis (<40 years) and (3) time to local recurrence less than 2 years. Nine percent of women received chemotherapy at the time of local recurrence. Conclusions: For breast cancer patients with a low baseline risk of mortality, the risk of death after an isolated local recurrence is substantial. Systemic treatment at the time of local recurrence needs further study.