[A case of distal bile duct carcinoma converted to neuroendocrine cancer and proliferated into the pancreas].

A woman in her 50s was referred due to a solid mass in the head of the pancreas. It was diagnosed as a neuroendocrine carcinoma (NEC) by endoscopic ultrasound-guided fine-needle aspiration. Consequently, pancreatoduodenectomy was performed. A well-differentiated adenocarcinoma component was revealed in the resected bile duct, suggesting a relationship with the NEC component in the pancreas. Genetic examination suggested that cholangiocarcinoma, but not coexisting carcinoma, was converted to NEC after the interstitial invasion. Finally, it was diagnosed as the NEC derived from the extrahepatic bile duct, which is rare at about 0.2-2% in gastrointestinal neuroendocrine neoplasms.

Proposal of intestinal tissue engineering combined with Bianchi's procedure.

AIM: The aim of this study is to examine the feasibility of the small intestinal submucosa (SIS) when the longitudinal staples during Bianchi's procedure are replaced with SIS graft. METHODS: The mesentery of the bowel was separated based on the bifurcated vessels in five beagles. A 2×7-cm longitudinal half of the bowel was excised and the defect was repaired using SIS with similar blood supply in Bianchi's operation. Six months later, intestinal motility in the SIS-grafted area was recorded. Tissue preparations were obtained from the reorganized area. An organ bath technique with electrical field stimulation was applied. Both the native small intestine and grafted area were morphologically investigated using immunohistochemistry. MAIN RESULTS: All dogs survived and thrived with no anastomotic leakage. Isoperistaltic migrating contractility during fasting was observed through the grafted segment including the reorganized area. The SIS-reorganized tissue contracted in response to an acetylcholine agonist and electrical field stimulation. The mucosa was covered with normal epithelium. Reorganization of neural and smooth muscle cells was observed. CONCLUSIONS: SIS has the potential for use as a scaffold that promotes the formation of a physical and physiological neointestine. Our present proposal approaches a novel surgical treatment in patients with short bowel syndrome.

Influence of mesenchymal stem cells on stomach tissue engineering using small intestinal submucosa.

Small intestinal submucosa (SIS) is a biodegradable collagen-rich matrix containing functional growth factors. We have previously reported encouraging outcomes for regeneration of an artificial defect in the rodent stomach using SIS grafts, although the muscular layer was diminutive. In this study, we investigated the feasibility of SIS in conjunction with mesenchymal stem cells (MSCs) for regeneration of the gastrointestinal tract. MSCs from the bone marrow of green fluorescence protein (GFP)-transgenic Sprague-Dawley (SD) rats were isolated and expanded ex vivo. A 1 cm whole-layer stomach defect in SD rats was repaired using: a plain SIS graft without MSCs (group 1, control); a plain SIS graft followed by intravenous injection of MSCs (group 2); a SIS graft co-cultured with MSCs (group 3); or a SIS sandwich containing an MSC sheet (group 4). Pharmacological, electrophysiological and immunohistochemical examination was performed to evaluate the regenerated stomach tissue. Contractility in response to a muscarinic receptor agonist, a nitric oxide precursor or electrical field stimulation was observed in all groups. SIS grafts seeded with MSCs (groups 3 and 4) appeared to support improved regeneration compared with SIS grafts not seeded with MSCs (groups 1 and 2), by enabling the development of well-structured smooth muscle layers of significantly increased length. GFP expression was detected in the regenerated interstitial tissue, with fibroblast-like cells in the seeded-SIS groups. SIS potently induced pharmacological and electrophysiological regeneration of the digestive tract, and seeded MSCs provided an enriched environment that supported tissue regeneration by the SIS graft in the engineered stomach.

Predictive biomarkers for the outcome of vaccination of five therapeutic epitope peptides for colorectal cancer.

BACKGROUND: We previously reported a phase I study of a cancer vaccine using five novel HLA-A*2402-restricted peptides, and demonstrated the safety and the promising potential of our five-peptide cocktail for advanced colorectal cancer. The objective of this analysis was to investigate predictive biomarkers for the prior selection of patients who are likely to have clinical benefit from such therapy. PATIENTS AND METHODS: Seventeen patients with colorectal cancer who were treated with the five peptides underwent a complete blood count, serum chemistry tests and enzyme-linked ImmunoSpot assay before the treatment as predictive markers of high reactivity to the peptides. RESULTS: Interleukin-6 level was a significant predictor for overall survival of patients treated with the peptide cocktail (p=0.017). A high neutrophil/lymphocyte ratio was likely to have some association with the poor induction of peptide-specific immune reaction. CONCLUSION: Interleukin-6 level might be a good predictive biomarker for clinical benefit of patients treated with this peptide vaccine.