Downregulated gene expression of TGF-βs in diabetic oral wound healing

BackgroundHealing of tooth extraction sockets in poorly controlled diabetic patients is often delayed and accompanied by severe infection. The exact cellular and molecular mechanisms underlying the pathogenesis of this complication are still not fully understood.ObjectivesThe purpose of this study was to investigate molecular changes associated with delayed oral wound healing in diabetes.Materials and methodsSix to eight weeks old male type 2 diabetes and age matched control inbred mice were used and maxillary molar tooth extractions were performed. At 4 and 7 days after tooth extraction, the edentulous mucosa of the mice were harvested, and analyzed for histology and gene expression of key wound healing factors.ResultsIn the diabetic model, histological analysis showed that epithelial tissue migration for wound closure was delayed after tooth extraction compared to the control. Quantitative real-time PCR revealed that expression of the TGF-β1, TGF-β2, TGF-β3, TGFβRII and TGFβRIII genes was significantly downregulated in the diabetic model at 4 and 7 days after tooth extraction.ConclusionThese results suggest that delayed wound healing of oral mucosa in diabetes may be associated with decreased expression levels of these regulatory genes which play important roles in controlling epithelial wound closure.     

Strategy to differentiate autoimmune pancreatitis from pancreas cancer

Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms. Based on histological and immunohistochemical examinations of various organs of AIP patients, AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease". Clinically, AIP patients and patients with pancreatic cancer share many features, such as preponderance of elderly males, frequent initial symptom of painless jaundice, development of new-onset diabetes mellitus, and elevated levels of serum tumor markers. It is of uppermost importance not to misdiagnose AIP as pancreatic cancer. Since there is currently no diagnostic serological marker for AIP, and approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological, and histopathological features. Findings suggesting AIP rather than pancreatic cancer include: fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed enhancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography, presence of other organ involvement such as bilateral salivary gland swelling, retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis; negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection.     

Synchronous double cancers of primary hepatic adenosquamous carcinoma and hepatocellular carcinoma: report of a case

A 76-year-old male was referred for the treatment of liver tumors detected by abdominal computed tomography (CT). Dynamic CT revealed a low-density tumor with an irregularly enhanced rim in the left lateral sector, and a highly enhanced, well-circumscribed tumor in the caudate lobe, accompanied by dilation of the intrahepatic biliary ducts in the left lobe. Preoperative imaging studies led to the diagnosis of double cancers consisting of intrahepatic cholangiocarcinoma and hepatocellular carcinoma (HCC). Left hemihepatectomy with caudate lobectomy was performed. The postoperative course was uneventful. Microscopic evaluation revealed that the tumor in the left lateral sector was adenosquamous carcinoma (ASC), whereas that in the caudate lobe was HCC. This report presents the first case describing the resection of synchronous double cancers of primary hepatic ASC and HCC.     

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.     

Is bariatric surgery safe in patients who refuse blood transfusion?

BackgroundA small, but significant, number of patients undergoing bariatric surgery refuse blood transfusion for religious or other personal reasons. Jehovah's Witnesses number more than 1 million members in the United States alone. The reported rates of hemorrhage vary from .5% to 4% after bariatric surgery, with transfusion required in one half of these cases. Pharmacologic prophylaxis against venous thromboembolism could further increase the perioperative bleeding risk. Our objective was to report the perioperative outcomes of bariatric surgery who refuse blood transfusion at a bariatric center of excellence, private practice in the United States.MethodsA retrospective review of all patients who refused blood transfusion when undergoing bariatric surgery during a 10-year period was conducted. Patients were identified from a prospectively maintained database by the bloodless surgery program at Legacy Good Samaritan Hospital. Data were collected on demographics, co-morbidities, laboratory values, medication use, blood loss, and 30-day complications.ResultsThirty-five bloodless surgery patients underwent bariatric surgery from 2000 to 2009. Of these 35 patients, 21 underwent laparoscopic adjustable gastric banding and 14 Roux-en-Y gastric bypass. Before 2006, only pneumatic compression devices were applied for venous thromboembolism prophylaxis (n = 6). Subsequently, combination venous thromboembolism prophylaxis was performed with fondaparinux sodium 2.5 mg for RYGB or enoxaparin 40 mg for LAGB (n = 29). One RYGB patient developed postoperative hemorrhage requiring reoperation. No venous thromboembolisms or deaths occurred.ConclusionBariatric surgery can be performed in patients who refuse blood transfusion with acceptable postoperative morbidity. Larger studies are necessary to confirm the safety of this approach and to examine the effect of pharmacologic thromboprophylaxis in this patient group.     

Nonanastomotic rupture of thoracic aortic Dacron graft treated by endovascular stent graft placement

A 61-year-old man had a Stanford type A acute aortic dissection, and the total aortic arch was replaced with 22-mm knitted Dacron graft in 1996. In 2006, he underwent mitral valve replacement and tricuspid valve repair due to severe mitral and tricuspid valve regurgitation. Although preoperative computed tomography (CT) scan suggested pseudoaneurysm around the Dacron graft replaced with aortic arch, it could not be repaired concomitantly. Four months later, in view of the technical difficulties of an open surgical procedure, the prosthetic graft failure was repaired by endovascular stent graft consisting of a Gianturco Z stent covered with an UBE woven Dacron graft. However, during a follow-up, aneurysm sac diameter increased without any sings of endoleak in follow-up CT scans. Redo endovascular stent graft placement using a Gore-TAG device was performed. Subsequently, shrinkage of the pseudoaneurysmal sac could be observed.     

Ultrasound evaluation of fetal brain dysfunction based on behavioral patterns

To identify fetuses at high risk of poor neurological outcomes using a novel ultrasound evaluation system. We assessed an ultrasound evaluation system based on our previous findings, consisting of screening for decreased or lack of fetal movements, abnormal patterns of fetal heart rate, congenital CNS malformations, polyhydramnios of unknown cause, and a “brief ultrasound evaluation” of fetal brain functions, including movement of extremities, breathing movements, ultradian rhythm, REM period, and NREM period. We then assessed the correlation between fetal brain functions and neurological outcomes in infancy (MR, CP, and low Developmental Quotient). During screening, we prospectively evaluated 4978 fetuses receiving prenatal and intrapartum management between January 2000 and December 2009 in our hospital that were later delivered between 32 and 41 weeks’ gestation and identified 93 cases as suspicious for impairment. Of the 93 fetuses, 26 underwent the second step of brief ultrasound examination at 35–40 weeks’ gestation. Our findings revealed that this method was adequately sensitive (80%) and specific (88%) in identifying neurological impairment. We concluded that this method was mainly useful in the clinical setting for establishing the first indication for fetal CNS examination for functional impairment, rendering it suitable for clinical application.