A case of 18 years disease-free survival after combined pancreatoduodenectomy and hemicolectomy for carcinosarcoma of the transverse colon.

BACKGROUND: Ascertaining the origin of large tumors located in the region of the pancreas head and adjacent mesocolon can pose a challenge preoperatively. En bloc pancreatoduodenectomy with hemicolectomy is often required towards curative tumor resection (R0) of malignant tumors in this region. CASE PRESENTATION: Herein we report a case of a 48-year-old man with two contiguous masses each 5 cm in size, located in the pancreatic head. The masses were detected incidentally by abdominal ultrasonography at an annual health check. Endoscopic biopsies revealed inflammation with no malignancy. Cross-sectional imaging showed the tumor direct invasion of the uncinate process of the pancreas, and the third portion of the duodenum. Based on imaging, a malignant submucosal tumor originating from mesenchymal cells in the mesentery of the transverse colon was made preoperatively. The mass required en bloc pancreatoduodenectomy, right hemicolectomy, and resection of the superior mesenteric vein. The final pathology was carcinosarcoma of the transverse colon. The patient survived 18 years after surgery without recurrence. CONCLUSIONS: Malignant tumors located in the region of the pancreas head should be considered for an en bloc curative tumor resection and adjuvant chemotherapy treatments offered that might be beneficial for carcinosarcoma.

Clinical Effects of a Pectin-Containing Oligomeric Formula in Tube Feeding Patients: A Multicenter Randomized Clinical Trial.

BACKGROUND: A pectin-containing oligomeric formula (POF) is a unique type of enteral formula that transforms from a liquid to a gel after reacting with gastric acid. Reports on its clinical effects have been limited. The present study was conducted to examine and verify the clinical effects of POF. METHODS: The study subjects were 201 stable patients receiving intragastric tube feeding. They were randomized into 2 groups to receive either POF or a standard polymeric formula (SPF) as a control. The duration of observation was 1 week. Analyses were conducted for the incidence of predefined composite events, including diarrhea, defecation treatments, and other enteral nutrition (EN) management-related events. RESULTS: Composite events occurred in 15 of 98 patients in the POF group and 30 of 100 patients in the SPF group, with a significantly lower incidence in the POF group compared with the SPF group (P = 0.011). In particular, diarrhea occurred in 2 patients in the POF group and 13 patients in the SPF group, with a significantly lower incidence in the POF group compared with the SPF group (P = 0.003). CONCLUSIONS: The results of this study suggest that POF is less likely to cause EN-related events, especially diarrhea, than SPF is.

[A case of successful S-1 alternate-day administration for far-advanced remnant gastric cancer].

A 81-year-old man presented with anemia. He received a distal gastrectomy for gastric ulcer as a 40-year-old, and was also diagnosed with prostate cancer with bone metastasis as an 80-year-old. He has been undergoing treatment with anti-androgen therapy. Gastrointestinal endoscopic examination showed advanced gastric cancer, which was diagnosed as poorly differentiated adenocarcinoma. Computed tomography(CT)showed enlarged para-aortic lymph nodes. The clinical Stage was IV: cT3, N3, M1. He was treated with oral S-1 alternate-day administration of 100mg/day. The tumor in his remnant stomach shrunk in size by 3 months after beginning S-1 administration, and an endoscopic examination revealed a scar, but no cancer cells were found in a biopsy specimen of the scar tissue. Furthermore, CT scan showed that the swollen para-aortic lymph nodes were obviously reduced in size. As a result, we diagnosed this as a partial response to chemotherapy with S-1 alternate-day administration. No adverse events during the treatment were due to S-1 administration. His quality of life and poor food intake remarkably improved. S-1 alternate-day therapy demonstrated efficacy and tolerable toxicity even for a patient who was elderly and /or with poor performance status. S-1 can be managed safely on an outpatient basis without side effects for a long duration, and has been superior in terms of continuity of treatment.

Endothelial cell promotion of early liver and pancreas development.

Different steps of embryonic pancreas and liver development require inductive signals from endothelial cells. During liver development, interactions between newly specified hepatic endoderm cells and nascent endothelial cells are crucial for the endoderm's subsequent growth and morphogenesis into a liver bud. Reconstitution of endothelial cell stimulation of hepatic cell growth with embryonic tissue explants demonstrated that endothelial signalling occurs independent of the blood supply. During pancreas development, midgut endoderm interactions with aortic endothelial cells induce Ptf1a, a crucial pancreatic determinant. Endothelial cells also have a later effect on pancreas development, by promoting survival of the dorsal mesenchyme, which in turn produces factors supporting pancreatic endoderm. A major goal of our laboratory is to determine the endothelial-derived molecules involved in these inductive events. Our data show that cultured endothelial cells induce Ptf1a in dorsal endoderm explants lacking an endogenous vasculature. We are purifying endothelial cell line product(s) responsible for this effect. We are also identifying endothelial-responsive regulatory elements in genes such as Ptf1a by genetic mapping and chromatin-based assays. These latter approaches will allow us to track endothelial-responsive signal pathways from DNA targets within progenitor cells. The diversity of organogenic steps dependent upon endothelial cell signalling suggests that cross-regulation of tissue development with its vasculature is a general phenomenon.

An endothelial-mesenchymal relay pathway regulates early phases of pancreas development.

Understanding the tissue interactions that induce pancreatic progenitor cells from the embryonic endoderm provides insights into congenital malformations, tissue repair, and differentiating stem cells to a pancreatic fate. The specification of pancreatic progenitors within the dorsal endodermal epithelium has been thought to involve two phases of mesodermal interactions; first with the lateral plate mesoderm and notochord and then with aortic endothelial cells. Afterwards, branching morphogenesis of the pancreatic bud is induced by Isl-1-positive dorsal mesenchyme cells, whose growth is stimulated by factors in the circulation. Using mouse genetic models and embryo tissue explants, we show that the aortic endothelium and dorsal mesenchyme each possess an additional role in pancreatic induction, prior to the branching morphogenesis step. Specifically, we find that aortic endothelial cells promote the survival of nearby, Isl-1-positive dorsal mesenchyme, independently of factors from the circulation. Furthermore, we find that FGF10 signaling from the mesenchyme cells maintains Ptf1a expression in the dorsal pancreatic bud and appears genetically redundant with a role for the transcription factor gene HNF6 in promoting the induction of Pdx-1-positive dorsal endoderm. Together, these studies reveal a relay pathway from aortic endothelium to dorsal mesenchyme and then to the endoderm, along with functions of the dorsal mesenchyme that promote the initial differentiation of the dorsal pancreatic endoderm, prior to organ morphogenesis.

Interaction of ATP sensor, cAMP sensor, Ca2+ sensor, and voltage-dependent Ca2+ channel in insulin granule exocytosis.

ATP, cAMP, and Ca(2+) are the major signals in the regulation of insulin granule exocytosis in pancreatic beta cells. The sensors and regulators of these signals have been characterized individually. The ATP-sensitive K(+) channel, acting as the ATP sensor, couples cell metabolism to membrane potential. cAMP-GEFII, acting as a cAMP sensor, mediates cAMP-dependent, protein kinase A-independent exocytosis, which requires interaction with both Piccolo as a Ca(2+) sensor and Rim2 as a Rab3 effector. l-type voltage-dependent Ca(2+) channels (VDCCs) regulate Ca(2+) influx. In the present study, we demonstrate interactions of these molecules. Sulfonylurea receptor 1, a subunit of ATP-sensitive K(+) channels, interacts specifically with cAMP-GEFII through nucleotide-binding fold 1, and the interaction is decreased by a high concentration of cAMP. Localization of cAMP-GEFII overlaps with that of Rim2 in plasma membrane of insulin-secreting MIN6 cells. Localization of Rab3 co-incides with that of Rim2. Rim2 mutant lacking the Rab3 binding region, when overexpressed in MIN6 cells, is localized exclusively in cytoplasm, and impairs cAMP-dependent exocytosis in MIN6 cells. In addition, Rim2 and Piccolo bind directly to the alpha(1)1.2-subunit of VDCC. These results indicate that ATP sensor, cAMP sensor, Ca(2+) sensor, and VDCC interact with each other, which further suggests that ATP, cAMP, and Ca(2+) signals in insulin granule exocytosis are integrated in a specialized domain of pancreatic beta cells to facilitate stimulus-secretion coupling.

Piccolo, a Ca2+ sensor in pancreatic beta-cells. Involvement of cAMP-GEFII.Rim2. Piccolo complex in cAMP-dependent exocytosis.

We have previously shown that cAMP-binding protein cAMP-guanidine nucleotide exchange factor II (GEFII) (or Epac2) interacting with Rim2 is involved in cAMP-dependent, protein kinase A-independent exocytosis in pancreatic beta-cells. The action of the cAMP-GEFII.Rim2 complex requires both intracellular cAMP and Ca(2+). Although Rim2 has C(2) domains, its role as a Ca(2+) sensor has remained unclear. In the present investigation, we have discovered that Piccolo, a CAZ (cytoskeletal matrix associated with the active zone) protein in neurons that is structurally related to Rim2, also binds to cAMP-GEFII and that it forms both homodimer and heterodimer with Rim2 in a Ca(2+)-dependent manner, whereas Rim2 alone does not form the homodimer. The association of Piccolo.Rim2 heterodimerization is stronger than Piccolo. Piccolo homodimerization. Treatment of pancreatic islets with antisense oligodeoxynucleotides against Piccolo inhibits insulin secretion induced by cAMP analog 8-bromo-cyclic AMP plus high glucose stimulation. These results suggest that Piccolo serves as a Ca(2+) sensor in exocytosis in pancreatic beta-cells and that the formation of a cAMP-GEFII.Rim2. Piccolo complex is important in cAMP-induced insulin secretion. In addition, this study suggests that CAZ proteins similar to those in neurons are also function in pancreatic beta-cells.