Recent evidence suggests that resistant starch (RS) is the single most important substrate for bacterial carbohydrate fermentation in the human colon. During two 4-wk periods. 12 healthy volunteers consumed a controlled basal diet enriched with either amylomaize starch (55.2 +/- 3.5 g RS/d; high-RS diet) or available cornstarch (7.7 +/- 0.3 g RS/d; low-RS diet). Approximately 90% of the RS consumed disappeared during intestinal passage; increased fermentation was verified by elevated breath-hydrogen excretion. During the high-RS diet, fecal wet and dry weight increased 49% and 56%, respectively (P < or = 0.005), whereas stool water content did not change significantly. Fecal concentrations and daily excretion of short-chain fatty acids were not different in the two study periods. During the high-RS diet, bacterial beta-glucosidase activity decreased by 26% (P < or = 0.05). Fecal concentrations of total and secondary bile acids were significantly lower during the high-RS than during the low-RS period [a decrease of 30% (P < or = 0.05) and 32% (P < or = 0.01), respectively, in total and secondary bile acids] whereas concentrations of primary bile acids were unaffected by RS consumption. During the high-RS diet, fecal concentrations of total neutral sterols decreased by 30% (P < or = 0.005) and fecal concentrations of 4-cholesten-3-one decreased by 36% (P < or = 0.05). These data suggest that RS has potentially important effects on bacterial metabolism in the human colon that may be relevant for cancer prevention.

Liver resection is a curative treatment for hepatocellular carcinoma (HCC). Tumor-infiltrating leukocytes (TILs) are important players in predicting HCC recurrence. However, the invasive margin could not be confirmed as relevant for HCC. The migration of immune cells into HCC may originate from intratumoral vessels. No previous study has examined perivascular (PV) infiltration. Tumors from 60 patients were examined. Immunohistochemistry was performed against CD3, CD8, CD20, and CD66b. TILs were counted in the PV regions using an algorithm for quantification of the tumor immune stroma (QTiS). The results were correlated with overall (OS) and disease-free survival (DFS), clinical parameters, and laboratory values. PV infiltration of TILs was predominant in resected HCC. Higher PV infiltration of CD3+ (p = 0.016) and CD8+ (p = 0.028) independently predicted better OS and DFS, respectively. CD20+ showed a trend towards better DFS (p = 0.076). Scoring of CD3+, CD8+, and CD20+ independently predicted OS and DFS (p < 0.01). The amount of perivascular-infiltrating CD3+ cells is an independent predictor of better OS, and CD8+ cells independently predict prolonged DFS. Our novel perivascular infiltration scoring (PVIS) can independently predict both DFS and OS in resected HCC patients.

Introduction: Current practice to only prioritize hepatocellular carcinoma (HCC) that fulfill the Milan criteria (IN MC) is changing, since it causes the exclusion of patients who could benefit from liver transplantation. To select patients outside MC (OUT MC) for transplantation, we implemented extended selection criteria without up-front morphometric restrictions containing surrogate parameters of tumor biology. Methods: OUT MC patients were considered without restrictions of morphometrics and received locoregional treatment after interdisciplinary consultation. Our dynamic selection criteria for OUT MC patients required (IN MUC): (1) treatment response over (2) at least 6 months and (3) alpha-fetoprotein ≤400 ng/mL over the entire evaluation period. Patients with IN MC tumors served as control and internal validation cohort. Results: 31 of 170 liver transplant candidates were OUT MC. Of these, 8 dropped out. The remaining 23 patients met the selection criteria and underwent transplantation. Recurrence-free survival was higher in patients transplanted IN MC compared to those OUT MC IN MUC (92.2% vs. 70.8%; p = 0.026) after 5 years of follow-up. Overall survival showed no significant difference (p = 0.552). With dynamic selection of transplant candidates, recurrence could also be predicted for the IN MC patients as internal validation cohort (c-index: 0.896; CI 0.588-0.981, p = 0.005). Conclusion: Dynamic selection criteria for the stratification of patients with OUT MC HCCs is feasible and allows for excellent long-term results and acceptable tumor recurrence rates comparable to IN MC patients.

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