Impact of lymph node metastasis on survival in patients with pathological T1 carcinoma of the ampulla of vater

To determine the prognostic factors for patients with pathological T1 (pT1) carcinoma of the ampulla of Vater, 36 consecutive patients with carcinoma of the ampulla of Vater who underwent surgery were retrospectively analyzed in terms of clinicopathological features. The overall 5-year Kaplan-Meier survival in all patients was 50.2%, and the median survival of all patients was 64.0 months. Factors favorably influencing a long-term outcome were the absence of lymph node metastasis (P<0.0001), the absence of ulcer formation of the tumor (P=0.0062), and the absence of tumor invasion into the duodenum (P = 0.0025) and the pancreas (P=0.0098). In a multivariate analysis, lymph node metastasis was the only predictor of survival (P=0.0023). In the pT1 stage patients, 20% of the patients had lymph node metastasis, and their survival was statistically poor compared to the pT1 patients without lymph node metastasis (P=0.017). As for survival after the operation, there was no significant difference between pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy.     

Neuroprotective effects of propofol in models of cerebral ischemia: inhibition of mitochondrial swelling as a possible mechanism

BACKGROUND: Propofol (2,6-diisopropylphenol) has been shown to attenuate neuronal injury in a number of experimental conditions, but studies in models of cerebral ischemia have yielded conflicting results. Moreover, the mechanisms involved in its neuroprotective effects are yet unclear. METHODS: The authors evaluated the neuroprotective effects of propofol in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. To investigate its possible mechanism of action, the authors then examined whether propofol could reduce Ca2+-induced rat brain mitochondrial swelling, an index of mitochondrial membrane permeability, as well as the mitochondrial swelling evoked by oxygen-glucose deprivation in CA1 pyramidal cells by transmission electron microscopy. Finally, they evaluated whether propofol could attenuate the infarct size and improve the neurobehavioral outcome in rats subjected to permanent middle cerebral artery occlusion in vivo. RESULTS: When present in the incubation medium during oxygen-glucose deprivation and the subsequent 24 h recovery period, propofol (10-100 microM) attenuated CA1 injury in hippocampal slices in vitro. Ca2+-induced brain mitochondrial swelling was prevented by 30-100 microM propofol, and so were the ultrastructural mitochondrial changes in CA1 pyramidal cells exposed to oxygen-glucose deprivation. Twenty-four hours after permanent middle cerebral artery occlusion, propofol (100 mg/kg, intraperitoneal) reduced the infarct size by approximately 30% when administered immediately after and up to 30 min after the occlusion. Finally, propofol administered within 30 min after middle cerebral artery occlusion was unable to affect the global neurobehavioral score but significantly preserved spontaneous activity in ischemic rats. CONCLUSIONS: These results show that propofol, at clinically relevant concentrations, is neuroprotective in models of cerebral ischemia in vitro and in vivo and that it may act by preventing the increase in neuronal mitochondrial swelling.     

Preoperative evaluation of the extrahepatic bile duct structure for laparoscopic cholecystectomy

Background The incidence of aberrant bile duct injury associated with laparoscopic cholecystectomy (LC) has not yet been adequately examined. This study aimed to clarify the types of normal cystic ducts and the incidence of aberrant extrahepatic bile ducts, and to search for a method of avoiding injuries during LC. Methods Aberrant hepatic ducts were retrospectively categorized into five types according to the pattern of the cystic ducts and the accessory hepatic ducts by preoperative endoscopic retrograde cholangiography or multidetector three-dimensional computed tomography using drip infusion cholangiography. The aberrant bile ducts were classified as type A (merging at the right side of the common bile duct), type B (merging at the anterior side), or type C (merging at the posterior left side). Results The intrahepatic bile ducts and cystic duct were clearly shown for 1,044 of the 1,278 patients who underwent LC. Secondary branches of aberrant cystic ducts were observed in 37 cases (3.5%), and accessory hepatic ducts were observed in 30 cases (2.9%). A comparison of the difficulties encountered with LC for each type based on the merging patterns of cystic ducts showed that type C needed a much longer operation time for LC than the other types. Conclusions A preoperative evaluation of the bile duct tract and the accessory hepatic duct before LC is important. Patients with a cystic duct merging normally into the posterior left side of the common hepatic duct (type C) experienced difficulty when undergoing LC. The authors have safely performed LC with the use of an endoscopic nasobiliary drainage tube in type D cases (cystic duct merging with the right hepatic duct), in type IV cases (cystic duct merging with an accessory hepatic duct).     

Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model

Transplantation of mesenchymal stem cells (MSCs) inhibits the progression of disc degeneration in animal models. We know of no study to determine the optimal number of cells to transplant into the degenerated intervertebral disc (IVD). To determine the optimal donor cell number for maximum benefit, we conducted an in vivo study using a canine disc degeneration model. Autologous MSCs were transplanted into degenerative discs at 10⁵, 10⁶, or 10⁷ cells per disc. The MSC‐transplanted discs were evaluated for 12 weeks using plain radiography, magnetic resonance imaging, and gross and microscopic evaluation. Preservation of the disc height, annular structure was seen in MSC‐transplantation groups compared to the operated control group with no MSC transplantation. Result of the number of remaining transplanted MSCs, the survival rate of NP cells, and apoptosis of NP cells in transplanted discs showed both structural microenvironment and abundant extracellular matrix maintained in 10⁶ MSCs transplanted disc, while less viable cells were detected in 10⁵ MSCs transplanted and more apoptotic cells in 10⁷ MSCs transplanted discs. The results of this study demonstrate that the number of cells transplanted affects the regenerative capability of MSC transplants in experimentally induced degenerating canine discs. It is suggested that maintenance of extracellular matrix by its production from transplanted cells and/or resident cells is important for checking the progression of structural disruption that leads to disc degeneration. Published by Wiley Periodicals, Inc. J Orthop Res 28:1267–1275, 2010     

Delayed accumulation of activated macrophages and inhibition of remyelination after spinal cord injury in an adult rodent model

OBJECT: Inhibition of remyelination is part of the complex problem of persistent dysfunction after spinal cord injury (SCI), and residual myelin debris may be a factor that inhibits remyelination. Phagocytosis by microglial cells and by macrophages that migrate from blood vessels plays a major role in the clearance of myelin debris. The object of this study was to investigate the mechanisms underlying the failure of significant remyelination after SCI. METHODS: The authors investigated macrophage recruitment and related factors in rats by comparing a contusion model (representing contusive SCI with residual myelin debris and failure of remyelination) with a model consisting of chemical demyelination by lysophosphatidylcholine (representing multiple sclerosis with early clearance of myelin debris and remyelination). The origin of infiltrating macrophages was investigated using mice transplanted with bone marrow cells from green fluorescent protein-transfected mice. The changes in levels of residual myelin debris and the infiltration of activated macrophages in demyelinated lesions were investigated by immunostaining at 2, 4, and 7 days postinjury. To investigate various factors that might be involved, the authors also investigated gene expression of macrophage chemotactic factors and adhesion factors. RESULTS: Activated macrophages coexpressing green fluorescent protein constituted the major cell population in the lesions, indicating that the macrophages in both models were mainly derived from the bone marrow, and that very few were derived from the intrinsic microglia. Immunostaining showed that in the contusion model, myelin debris persisted for a long period, and the infiltration of macrophages was significantly delayed. Among the chemotactic factors, the levels of monocyte chemoattractant protein-1 and granulocyte-macrophage colony-stimulating factor were lower in the contusion model at 2 and 4 days postinjury. CONCLUSIONS: The results suggest that the delayed infiltration of activated macrophages is related to persistence of myelin debris after contusive SCI, resulting in the inhibition of remyelination.     

Intramuscular hemangioma of the upper extremity in infants and children

PURPOSE: Intramuscular hemangiomas (IMHs) are benign tumors comprising just 0.8% of all hemangiomas and are extremely rare in the upper limbs. These tumors can pose diagnostic as well as therapeutic challenges for orthopaedic surgeons, especially in younger children. We reviewed cases of IMH of the upper extremity in infants and children from our institute. METHODS: Six consecutive patients underwent surgical treatment for IMH in our hospital. There were 4 girls and 2 boys. Long-standing pain and swelling were common symptoms except in a 1-year-old boy. Tumors were evaluated by radiography, computed tomography, magnetic resonance imaging, and angiography. RESULTS: After a mean follow-up of 42 months, all patients except one were free of pain and without tumor recurrence or functional impairment. Minimal symptoms remained in a 6-year-old boy who underwent biopsy only. CONCLUSION: Magnetic resonance imaging is the most useful evaluation for IMH because it not only delineates the extent of tumor but also reveals characteristic structures. For young children with IMH, wide excision is the treatment of choice to prevent local recurrence, but every patient should be treated individually after evaluating the patient's age, tumor location and invasion, and cosmetic considerations. LEVEL OF EVIDENCE: Therapeutic study-level III.     

New titanium spacer for cervical laminoplasty: initial clinical experience. Technical note

Many commercially available hydroxyapatite (HA) spacers for cervical laminoplasty have been introduced but have disadvantages such as lack of plasticity, easy cracking, and occasional difficulty in fixation by sutures. Here we present the short-term results of a newly designed titanium spacer (Laminoplasty Basket) in open-door cervical laminoplasty, and evaluated clinically and radiologically. The titanium box-shaped spacer with two arms for fixation was easily inserted and fixed into the laminoplasty space with 4-mm or 5-mm length screws after the posterior cervical arch was repositioned for the canal expansion. Twenty-one patients with cervical myelopathy due to spondylosis or ossification of the longitudinal ligament or developmental narrow canal observed for more than 6 months postoperatively were enrolled in this study. The neurological condition of these patients improved from 9.4 points on the Japanese Orthopaedic Association scale preoperatively to 13.5 points at 6 months after surgery. Postoperative radiological evaluation showed no laminar closure or implant failure and cervical spine curvature was maintained. These results seemed to have no significant difference compared with those using HA spacers. This titanium spacer is a potential substitute for conventional HA or other similar devices in cervical laminoplasty.     

Enrichment for murine keratinocyte stem cells based on cell surface phenotype

The identification and physical isolation of epithelial stem cells is critical to our understanding of their growth regulation during homeostasis, wound healing, and carcinogenesis. These stem cells remain poorly characterized because of the absence of specific molecular markers that permit us to distinguish them from their progeny, the transit amplifying (TA) cells, which have a more restricted proliferative potential. Cell kinetic analyses have permitted the identification of murine keratinocyte stem cells (KSCs) as slowly cycling cells that retain [(3)H]thymidine ([(3)H]Tdr) label, termed label-retaining cells (LRCs), whereas TA cells are visualized as rapidly cycling cells after a single pulse of [(3)H]Tdr, termed pulse-labeled cells (PLCs). Here, we report on the successful separation of KSCs from TA cells through the combined use of in vivo cell kinetic analysis and fluorescence-activated cell sorting. Specifically, we demonstrate that murine dorsal keratinocytes characterized by their high levels of alpha(6) integrin and low to undetectable expression of the transferrin receptor (CD71) termed alpha(6)(bri)CD71(dim) cells, are enriched for epithelial stem cells because they represent a minor ( approximately 8%) and quiescent subpopulation of small blast-like cells, with a high nuclear:cytoplasmic ratio, containing approximately 70% of label-retaining cells, the latter being a well documented characteristic of stem cells. Conversely, TA cells could be enriched in a phenotypically distinct subpopulation termed alpha(6)(bri)CD71(bri), representing the majority ( approximately 60%) of basal keratinocytes that are actively cycling, and importantly contain approximately 70% of [(3)H]Tdr pulse-labeled cells. Importantly, immunostaining of dorsal skin revealed the presence of CD71(dim) cells in the hair follicle bulge region, a well documented location for KSCs.