Bone marrow stem cells for urologic tissue engineering

OBJECTIVES: Experiments in rats and dogs have demonstrated the potential of bone marrow-derived mesenchymal stem cells (MSCs) for urinary tract tissue engineering. However, the small graft size in rats and a failure to identify the MSCs in engineered tissues made it difficult to assess the true potential of these cells. Our goals were to characterize MSCs from pigs, determine their ability to differentiate into smooth muscle cells (SMCs) and use them in an autologous augmentation cystoplasty. METHODS: MSCs were isolated from pigs and analyzed for common markers of MSCs by flow cytometry. SMC differentiation was determined by immunoblotting. MSCs were isolated, genetically labeled, expanded in vitro, seeded onto small intestinal submucosa (SIS) and used for autologous bladder augmentation. RESULTS: Porcine MSCs are morphologically and immunophenotypically similar to human MSCs. Culturing MSCs at low density enhances proliferation rates. MSCs consistently differentiate into mature SMCs in vitro when maintained at confluence. Labeled MSCs grew on SIS over one week in vitro and survived a 2-week implantation as an autologous bladder augment in vivo. Some label-positive cells with SMC morphology were detected, but most SMCs were negative. Notably, many cells with a urothelial morphology stained positively. CONCLUSIONS: Porcine MSCs have similar properties to MSCs from other species and consistently undergo differentiation into mature SMC in vitro under specific culture conditions. Labeled MSCs within SIS may assist tissue regeneration in augmentation cystoplasty but may not significantly incorporate into smooth muscle bundles.     

Bone development in female rats maintained with soy-free or soy-containing food as determined by computer-assisted tomography and serum bone markers

The development of bone in immature rats and in aged rats has not been thoroughly studied. Therefore, we investigated the development of bones in young, middle-aged, and aged female rats. Because most rat chows contain soy proteins, including estrogenic isoflavones, as a source of protein, comparison of effects on mineral density and on areas of the cancellous and cortical parts of the metaphysis of the tibia as measured by quantitative computer tomography in animals fed with soy-free and soy-containing food was made. As surrogate parameters of bone metabolism serum, osteocalcin (OC) and the breakdown products of bone collagen--the Crosslaps--were also determined. The cancellous density increased between day 25 after birth to reach peak bone mass at 90 days of age; in 18-and 20-month-old animals, significant reduction was observed that was more profound in the animals fed with soy-free food. Serum OC and the Crosslaps were highest in 15-day-old and lowest in 9-, 18-, and 20-month-old animals. Animals fed with soy-containing food had significantly higher osteocalcin levels at day 15 and at 9 and 18 months of age. In the aged animals, intake of soy isoflavones that have an estrogenic effect appears to exert beneficial effects as these aged animals lost less cancellous bone, as indicated by their surrogate parameters of metabolism in the serum. It is concluded that exorbitantly high bone turnover is present in immature and peripubertal rats. Raising and keeping female rats under soy-free or soy-containing conditions has marked effects on several bone parameters that are of particular relevance in aged animals.     

Current status of coronary artery bypass grafting

The number of cases of coronary artery bypass grafting (CABG) reached more than 21 000 in Japan in 2002, and the operative mortality decreased to less than 1%, including emergency operations. The annual number of CABGs in Japan declined 17% after 2003 to 18 000 cases in 2005 owing to unrestricted percutaneous coronary intervention (PCI) with drug-eluting stents. However, CABG is the best treatment for multivessel coronary artery disease based on the comparative data of PCI versus CABG. There have been two trends in CABG during the last decade. One is the widespread use of off-pump (OP) CABG, and the other is multiple coronary artery revascularization. In 2004 and 2005, approximately 60% of all isolated CABG procedures in Japan were performed without cardiopulmonary bypass. In a study of long-term outcomes comparing PCI with drug-eluting stents versus CABG with only arterial grafts, the latter was carried out in 52% of total cases and in 66% of OPCAB cases. OPCAB with multiple arterial grafts has become the standard CABG in Japan.     

Role of ErbB4 in Breast Cancer

Members of the ErbB subfamily of receptor tyrosine kinases are important regulators of normal mammary gland physiology, and aberrations in their signaling have been associated with breast tumorigenesis. Therapeutics targeting epidermal growth factor receptor (EGFR = ErbB1) or ErbB2 in breast cancer have been approved for clinical use. In contrast, relatively little is known about the biological significance of ErbB4 signaling in breast cancer. This review focuses on recent advances in our understanding about the role of ErbB4 in breast carcinogenesis, as well as in the potential clinical relevance of ErbB4 in breast cancer prognostics and therapy.     

Intraoperative Allogeneic Red Blood Cell Transfusion in Ampullary Cancer Outcome after Curative Pancreatoduodenectomy: A Clinical Study and Meta-Analysis

BACKGROUND: Allogeneic blood transfusion (ABT) containing packed red blood cells (RBCs) has a known immunosuppressive effect that may affect cancer metastases and recurrence. This study examined whether intraoperative allogeneic RBC transfusion is an independent risk factor of adverse outcome in patients with ampullary carcinoma after curative pancreatoduodenectomy. METHODS: The clinical data of 67 patients with carcinoma of the ampulla of Vatar underwent pancreatoduodenectomy between 1999 and 2004 were analyzed, and long-term follow-up visits were made for all patients. Kaplan-Meier statistics and Cox proportional hazard methodology were used to perform univariate and multivariate analysis to identify independent risk factors for survival. For the meta-analysis, all English-language studies regarding blood transfusion from carcinoma of the ampulla of Vatar or ampullary carcinoma and prognostic factors or factors for survival from 1995 to 2007 were reviewed, and contingency tables were constructed from which a summary relative risk was calculated. RESULTS: There were 43 patients (64.2%) who received an intraoperative ABT. The amount of intraoperative ABT ranged from 2 to 13 (mean, 4.25) units; there were 18 patients transfused at 2 units, and 25 patients transfused >/=3 units. The follow-up ranged from 2 to 90 (mean, 49) months. Forty-five patients (67.2%) died as a result of tumor progression. For patients transfused >/=3 units, median and cumulative 3-year and 5-year survivals were poorer significantly than that of patients transfused with 2 units and/or nontransfused patients (P < 0.05). After multivariate analysis, except for presence of lymph node metastasis (P = 0.023) and pancreatic invasion (P = 0.024), the intraoperative ABT >/=3 units was found to be an independent poor prognostic factor for those with ampullary cancer after curative pancreatoduodenectomy either (relative risk, 2.082; 95% confidence interval (CI), 1.048-4.135; P = 0.036). Meta-analysis of 346 patients showed the summary relative risk of an adverse outcome after intraoperative ABT in these studies was 2.55 (95% CI, 1.59-4.1). CONCLUSIONS: The amount of intraoperative ABT is one of the important factors that adversely influenced survival in patients with ampullary cancer after curative pancreatoduodenectomy. Healing anemia preoperatively and careful dissection to minimize intraoperative bleeding as much as possible are mandatory for reducing risk of the intraoperative ABT.     

Graduate Education in General Surgery and Its Related Specialties and Subspecialties in the United States

Each year, approximately 1,000 graduating medical students enter training in general surgery and its related specialties and subspecialties in the United States. Traditionally, residents who want to practice vascular surgery, plastic surgery, thoracic surgery, and other specialties and subspecialties derived from general surgery have been required to complete five years of training in general surgery before embarking on further training. However, three phenomena have recently emerged that are changing the picture of surgical training: (1) proliferation of fellowships in subspecialties of general surgery, (2) increasing desire of subspecialties of general surgery for recognition as specialties in their own right, and (3) pressure to reduce or eliminate the traditional general surgery training required before specialization or subspecialization. In the meantime, and perhaps as a consequence of these changes, traditional general surgery has become less attractive as a specialty and there has been significant concern about the quality of training in general surgery. As a result of fewer trainees electing general surgery as a career, there is now increasing evidence of a shortage of surgeons who are able to handle a reasonably broad caseload of emergency care in general surgery and trauma.Many of these issues are currently being addressed by the profession. Among the initiatives underway are developing a standardized curriculum in general surgery, appropriately apportioning operative experience between residency and fellowship, considering alternative pathways for training in subspecialties, and developing a system for oversight of advanced surgical training fellowships. The system for governance of graduate surgical education in the United States is less centralized than in other countries. One initiative that has been undertaken to improve coordination of efforts between educational and regulatory bodies is the formation of the Surgical Council on Resident Education (SCORE), a voluntary consortium of six organizations with the mission of defining a national curriculum for general surgery residency and with the goal of facilitating collaboration on educational issues involving general surgery and its related specialties and subspecialties.     

The Number of Metastatic Lymph Nodes is a Significant Risk Factor for Bone Metastasis and Poor Outcome After Surgery for Linitis Plastica-type Gastric Carcinoma

BACKGROUND: Linitis plastica-type gastric carcinoma remains a disease with poor prognosis despite an aggressive surgical approach. Although a prominent pattern of disease failure is peritoneal carcinomatosis, some patients experience rapid disease progression without signs of the peritoneal disease. METHODS: Clinicopathologic data from 178 patients with linitis plastica-type gastric cancer operated on between 1991 and 2000 were analyzed. Survival stratified by curability of surgery, pN stage, and patterns of failure were evaluated by using the Kaplan-Meier method, and chi(2) test was used to evaluate correlation between the number of metastatic lymph nodes in terms of pN categories and the incidence of various patterns of metastasis and recurrence. Cox regression hazard model was used to identify independent prognostic factors. RESULTS: R0 resection was performed only among 82 patients (46% of those who underwent laparotomy). Node metastasis was frequent with only 22 patients classified as pN0. Peritoneal carcinomatosis was observed in 131 patients and was the commonest pattern of recurrence. Bone metastasis, found in 13 patients, was associated with poor outcome, and its incidence was significantly correlated with the number of metastatic nodes. pT4 status and pN3 status were identified as significant independent prognostic determinants. CONCLUSION: Treatment strategy for the linitis plastica should in general combine surgery with aggressive treatment directed toward peritoneal disease. However, patients with >16 metastatic nodes more often are associated with bone metastasis than those with modest nodal involvement and suffer from poor prognosis.     

Outcome Analysis of Blood Product Transfusion in Trauma Patients: A Prospective,Risk-Adjusted Study

BACKGROUND: Studies have confirmed adverse outcome associated with transfusion of packed red blood cells (PRBCs) in trauma; however, little data are available regarding other blood product transfusion, such as fresh frozen plasma (FFP) and platelets. The objective of this study was to examine risk-adjusted outcome in trauma with stratification by blood product type. METHODS: Prospective data were collected daily for 1,172 consecutive trauma patients admitted to the intensive care unit (ICU) during a 2-year period, including transfusion rates of blood products (PRBCs, FFP, platelets). Outcome assessment included infection rate, ventilator days (Vdays), ICU and hospital length of stay (LOS), and mortality. RESULTS: Blood products were transfused in 786 (67%) patients. The study cohort had a mean age of 43 +/- 21 years and Injury Severity Score (ISS) of 24 +/- 13. Although the majority of patients were men, women were more likely to be transfused (p < 0.001). Mean transfusion rates of PRBCs (5.5 +/- 9.6 U), FFP (5.4 +/- 11.4), and platelets (3.7 +/- 11.1) were high. Univariate analysis identified that blood product transfusion (any type) was associated with a significantly greater infection rate (34% vs. 9.4%; p < 0.001), hospital LOS (18.6 vs. 9 days; p < 0.001), ICU LOS (13.7 vs. 7.4 days; p < 0.001), Vdays (12.9 vs. 6.3 days; p < 0.001), and mortality (19% vs. 8.3%; p < 0.001). Multivariate analysis (risk-adjusted for severity of injury by ISS, age, sex, and race, and stratified by blood product type) confirmed that risk of infection increased by 5%, and hospital LOS, ICU LOS, and Vdays increased by 0.64, 0.42, and 0.47 days, respectively, for every unit of PRBCs given. Risk of death increased by 3.5% for every unit of FFP transfused. CONCLUSION: There is a dose-dependent correlation between blood product transfusion and adverse outcome (increased mortality and infection) in trauma patients.     

Endoscopic endonasal approach to the ethmoidal planum: anatomic study

The endoscopic endonasal technique is currently used by otolaryngologists for the management of different extradural lesions located below the ethmoidal planum. The cooperation between ENTs and neurosurgeons has recently pushed the use of such approach also in the removal of some intradural lesions, which has promoted the interest for an anatomic study to identify the anatomical landmarks and the dangerous points during the endoscopic approach to this area. In six fresh cadaver heads, unilateral and bilateral measurements between the main landmarks of the approach were performed by means of an endoscopic endonasal approach. A wide exposure of the midline anterior skull base was realized. The maximum of lateral extension was obtained between the two medial orbital walls, at the middle of the cribriform plate (mean distance 25,33 mm), while the mean distance between the anterior and posterior ethmoidal arteries at the level of the lamina papyracea was 16 mm. The endoscopic endonasal route can be considered a minimally invasive technique to approach the ethmoidal planum. It requires adequate anatomical knowledge and endoscopic skill for its realization. Due to the wide window realizable through this corridor, it could be considered in selected cases for the removal of intradural lesions such as meningiomas or estesioneuroblastomas.     

Atypical presentation of distal renal tubular acidosis in two siblings

Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH <5.50 during systemic acidosis. We report two male siblings who presented with severe hyperchloremic metabolic acidosis, high urinary pH, nephrocalcinosis, growth retardation, sensorineural hearing loss, and hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy.