Postpancreatoduodenectomy Hemorrhage Treated by Combined Transcatheter Arterial Embolization and Superior Mesenteric Artery to Iliac Artery Bypass: Report of a Case

Postpancreatectomy hemorrhage is a potentially life-threatening complication. We report herein our experience with a 65-year-old man with locally advanced pancreatic adenocarcinoma who underwent pancreatoduodenectomy with lymphadenectomy following neoadjuvant chemoradiotherapy. On postoperative day 45, he developed massive hematemesis. Angiography revealed active bleeding from the common hepatic artery, and transcatheter coil embolization of that vessel was successfully performed. On postoperative day 64, he again developed massive hematemesis. Angiography revealed active bleeding from the proximal superior mesenteric artery. Immediately after coil embolization of that vessel, bypass grafting between the superior mesenteric artery and the right common iliac artery was performed, using a greater saphenous vein graft. The combination of embolization and bypass grafting is an option for treatment of bleeding from the superior mesenteric artery in an emergent situation.Key words: Superior mesenteric artery, Bleeding, Bypass, Pancreatoduodenectomy, Postpancreatectomy hemorrhagePostpancreatectomy hemorrhage (PPH) is a rare but life-threatening complication, often associated with the presence of a pancreatic fistula or intraabdominal abscess.¹ The mortality associated with arterial bleeding after pancreatoduodenectomy is reportedly between 14.3% and 30.7%.^2–6 With recent advances in interventional radiology techniques, transcatheter arterial embolization (TAE) has become an alternative to surgical treatment.^3,5,7,8 However, it may be difficult to treat these patients with interventional radiology techniques alone, given their often unstable condition. In addition, the inappropriate use of TAE for arterial bleeding, especially after pancreatoduodenectomy, can lead to end-organ infarction and subsequent infection. We report herein our experience with a patient who had bleeding from the superior mesenteric artery (SMA) after pancreatoduodenectomy. This patient was successfully treated using SMA coil embolization followed by creation of an SMA-iliac artery bypass using a greater saphenous vein graft.     

The eternal tooth germ is formed at the apical end of continuously growing teeth

Rodent incisors are known to be continuously growing teeth that are maintained by both the cell-proliferation at the apical end and the attrition of the incisal edge. This type of tooth had a special epithelial structure for the maintenance of stem cells, showing the bulbous epithelial protrusion at the apical end. The morphological transition of the epithelial-mesenchymal compartment by serial transverse sections of the apical end toward the incisal direction is likely to reflect the development of the tooth germ in the prenatal stage. Based on the present histological and previous molecular biological studies, the special structure at the apical end is obviously different from the cervical loop giving rise to Hertwig's epithelial root sheath (HERS), in human, mouse and rat molar tooth germs. Hence, we propose a new concept that the eternal tooth bud producing various dental progeny is formed at the apical end of continuously growing teeth, and a new term "apical bud" for indicating this specialized epithelial structure. Furthermore, BrdU labelling analysis suggested that the guinea-pig molars, which were continuously growing teeth, also possessed plural specific proliferative regions and "apical bud" at the apical end.     

Glycogen synthase kinase-3β opens mitochondrial permeability transition pore through mitochondrial hexokinase II dissociation

Accumulating evidence has revealed pivotal roles of glycogen synthase kinase-3β (GSK3β) inactivation on cardiac protection. Because the precise mechanisms of cardiac protection against ischemia/reperfusion (I/R) injury by GSK3β-inactivation remain elusive, we investigated the relationship between GSK3β-mediated mitochondrial hexokinase II (mitoHK-II; a downstream target of GSK3β) dissociation and mitochondrial permeability transition pore (mPTP) opening. In Langendorff-perfused hearts, GSK3β inactivation by SB216763 improved the left ventricular-developed pressure and retained mitoHK-II binding after I/R. In permeabilized myocytes, GSK3β depolarized mitochondrial membrane potential with accelerated mitochondrial calcein release (suggesting GSK3β-mediated mPTP opening) and decreased mitoHK-II bindings. GSK3β-mediated mPTP opening depended on mitoHK-II binding, i.e., it was accelerated by dissociation of mitoHK-II (dicyclohexylcarbodiimide) and attenuated by enhancement of mitoHK-II binding (dextran). However, inactivation of mitoHK-II by glucose-depletion or glucose-6-phosphate inhibited the GSK3β-mediated mPTP opening. We conclude that GSK3β-mediated mPTP opening may be involved in I/R injury and regulated by mitoHK-II binding and activity.     

TGF-β1 Promotes Lymphangiogenesis during Peritoneal Fibrosis

Peritoneal fibrosis (PF) causes ultrafiltration failure (UFF) and is a complicating factor in long-term peritoneal dialysis. Lymphatic reabsorption also may contribute to UFF, but little is known about lymphangiogenesis in patients with UFF and peritonitis. We studied the role of the lymphangiogenesis mediator vascular endothelial growth factor-C (VEGF-C) in human dialysate effluents, peritoneal tissues, and peritoneal mesothelial cells (HPMCs). Dialysate VEGF-C concentration correlated positively with the dialysate-to-plasma ratio of creatinine (D/P Cr) and the dialysate TGF-β1 concentration. Peritoneal tissue from patients with UFF expressed higher levels of VEGF-C, lymphatic endothelial hyaluronan receptor-1 (LYVE-1), and podoplanin mRNA and contained more lymphatic vessels than tissue from patients without UFF. Furthermore, mesothelial cell and macrophage expression of VEGF-C increased in the peritoneal membranes of patients with UFF and peritonitis. In cultured mesothelial cells, TGF-β1 upregulated the expression of VEGF-C mRNA and protein, and this upregulation was suppressed by a TGF-β type I receptor (TGFβR-I) inhibitor. TGF-β1–induced upregulation of VEGF-C mRNA expression in cultured HPMCs correlated with the D/P Cr of the patient from whom the HPMCs were derived (P<0.001). Moreover, treatment with a TGFβR-I inhibitor suppressed the enhanced lymphangiogenesis and VEGF-C expression associated with fibrosis in a rat model of PF. These results suggest that lymphangiogenesis associates with fibrosis through the TGF-β–VEGF-C pathway.The decrease in ultrafiltration capacity that is associated with the high peritoneal solute transport that is observed after prolonged peritoneal dialysis (PD) treatment is a major reason for its discontinuation.^1–4 Several studies have shown that a higher peritoneal solute transport rate is associated with reduced survival of PD patients.^1,2,5 The characteristic features of chronic peritoneal damage in PD treatment are associated with submesothelial fibrosis and neoangiogenesis.^6,7 Analyses of the surface peritoneum showed no significant changes in vessel density with duration of PD.^6,8 In addition, the vessel density in patients with ultrafiltration failure (UFF) was significantly higher than the vessel density in normal individuals or non-PD patients, but it was not higher than the vessel density in patients undergoing PD.⁶ These findings suggest that factors other than increased vascular density may be involved in disease states associated with increased transport of peritoneal membranes. In addition, the relationship between peritoneal fibrosis and UFF remains obscure.Blood capillaries have a continuous basal lamina with tight interendothelial junctions and are supported by pericytes and smooth muscle cells. In contrast, lymphatic capillaries are thin-walled with a wide lumen and do not contain pericytes or basement membrane. The structures of lymphatic vessels are suitable for the removal of tissue fluid, cells, and macromolecules from the interstitium.^9–11 If lymphangiogenesis develops in the peritoneal membrane, absorption of the PD fluid could be increased and lead to UFF. An increase in the number of lymphatic vessels has recently been reported in several disease conditions, including tumor metastasis,^12–15 chronic respiratory inflammatory diseases,^16–18 wound healing,¹⁹ and renal transplant rejection.^20,21 We recently reported that lymphangiogenesis had developed in tubulointerstitial fibrosis of human renal biopsy specimens,²² and we also reported the mechanisms of lymphangiogenesis in rat unilateral ureteral obstruction models.²³The lymphatic absorption rate, which is measured by the rate at which intraperitoneally administered radioactive serum albumin or macromolecule dextran 70 disappears, is significantly higher in patients with UFF, and lymphatic reabsorption is considered to be one of the causes of UFF.^24–27 However, the results from these clinical approaches have been controversial.^28,29 In addition, little is known about the pathology and the process of lymphangiogenesis in patients with UFF and peritonitis.In this study, we investigated lymphangiogenesis and the expression of vascular endothelial growth factor-C (VEGF-C), which is a potentially important mediator of lymphangiogenesis, in human peritoneal tissues, PD effluent, and peritoneal mesothelial cells. We also explored VEGF-C induction by TGF-β1 in the human mesothelial cell line (Met-5A) and cultured human peritoneal mesothelial cells (HPMCs) from the spent PD effluent of patients with varying rates of peritoneal transport. Finally, we explored the relationship between peritoneal fibrosis and lymphangiogenesis in rats that were administered chlorhexidine gluconate (CG) into the abdominal cavity, which provides a model of chemically induced peritoneal inflammation/fibrosis.^30–32 This work is the first report to show that lymphangiogenesis is linked to the peritoneal fibrosis that is often associated with a high peritoneal transport rate.     

Antimicrobial-induced release of endotoxin from Pseudomonas aeruginosa: comparison of in vitro and animal models

This study was designed to compare the amount of lipopolysaccharide (LPS) induced following exposure to doripenem, imipenem/cilastatin, meropenem and ceftazidime in an in vitro computerized-simulation system (simulating the drug concentration pattern in human plasma after administration of a drug), with that induced by exposure to a drug at a constant concentration. When Pseudomonas aeruginosa was exposed to the test drugs at constant concentrations of 0.1 x, 1 x and 10 x MIC, differential relative induction of LPS was observed as follows: ceftazidime > meropenem, doripenem > imipenem/cilastatin. In the computerized-simulation system, however, the amount of LPS induced by treatment with ceftazidime (1 g) was similar to that by doripenem (250 mg), imipenem/cilastatin (500 mg) and meropenem (500 mg). In a rat model of P. aeruginosa bacteraemia, rates of eradication of bacteria from the blood were similar for carbapenems and ceftazidime except for 1 h post-administration of ceftazidime. Serum LPS levels induced by treatment with doripenem (30 mg/kg), imipenem/cilastatin (30 mg/kg), meropenem/cilastatin (30 mg/kg) and ceftazidime (50 mg/kg) were almost the same at 3 h after administration of each drug. Data obtained from computerized-simulation systems might be more applicable than those obtained from organisms exposed to constant drug concentrations for estimating the amount of LPS in the plasma of human patients infected with Gram-negative bacteria.