Clinical assessment of efficacy of poly-L-lactide sternal pin on sternal stability and post-operative pain: a prospective randomized trial in cardiovascular surgery.

BACKGROUND: Although the incident rate is low, sternal dislocation and dehiscence due to unstable sternal fixation after cardiovascular surgery could cause potentially lethal complications. Thus, to enforce the stability of closed sternum, the sternal pins have been utilized at surgeon's discretion. However, there is no randomized clinical trial to test whether these pins are effective to stabilize a sternum. Hence, this study aimed to examine the clinical efficacy of bioabsorbable poly-L-lactide (PLLA) sternal pins in reinforcing sternal stability and preventing instability of the sternum after full sternotomy. METHODS: We conducted a single institutional, prospective, randomized, single-blinded clinical study involving 100 patients who underwent an initial cardiovascular surgery via sternotomy. Patients were randomly allocated into two groups: with (group P) and without (group N) PLLA sternal pins, at 1:1 ratio from November 2013 to April 2016. Sternal deviation and stability were assessed with postoperative computed tomography (CT) at two postures to put shear stress on the sternum. Additionally, information on patient demographic indices was obtained prospectively, and patient's pain intensity was assessed with numerical rating scoring system during rehabilitation. Furthermore, propensity score matching was performed for further comparative sub-analysis. RESULTS: Ninety-one patients (43 in group P and 48 in group N) were analyzed using the intention-to-treat method. Group N had a significantly higher proportion of males (P=0.015) and ischemic disease as a primary diagnosis (P=0.040) than group P. Postoperative CT showed that the degree of sternal deviation and stability were comparable between the groups. Similarly, the numerical rating score of pain during rehabilitation showed no difference between the groups. Even after adjusting for patient characteristics using propensity score matching method, no significant differences in sternal gaps, stability, and numerical rating score of pain were observed. Of note, no material-related adverse event such as wound infection was found. CONCLUSIONS: We could not identify the efficacy of the sternal pin in enforcing sternal stability based on CT measurements with mild shear stress on sternum after cardiovascular surgery. Nevertheless, our results with no adverse events might encourage further investigations with a more specific cohort who is susceptible to infection but requires an additional sternal fixation. TRIAL REGISTRATION: This study was registered in University Hospital Medical Information Network Clinical Trial Registry (UMIN000017357).

Exosomes of Epstein-Barr Virus-Associated Gastric Carcinoma Suppress Dendritic Cell Maturation.

The Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is characterized by the infiltration of lymphocytes and a unique tumor microenvironment. Exosomes from cancer cells are essential for intercellular communication. The aims of this study were to investigate the secretion of EBVaGC exosomes and their physiological effect on dendritic cell maturation in vitro and to characterize dendritic cells (DCs) in EBVaGC in vivo. Western blotting analysis of CD63 and CD81 of exosomes from EBV-infected gastric cancer cell lines indicated an increase in exosome secretion. The fraction of monocyte-derived DCs positive for the maturation marker CD86 was significantly suppressed when incubated with exosomes from EBV-infected gastric cancer cell lines. Immunohistochemical analysis of GC tissues expressing DC markers (S100, Langerin, CD1a, CD83, CD86, and BDCA-2) indicated that the density of DCs was generally higher in EBVaGC than in EBV-negative GC, although the numbers of CD83- and CD86-positive DCs were decreased in the group with high numbers of CD1a-positive DCs. A low number of CD83-positive DCs was marginally correlated with worse prognosis of EBVaGC in patients. EBVaGC is a tumor with abundant DCs, including immature and mature DCs. Moreover, the maturation of DCs is suppressed by exosomes from EBV-infected epithelial cells.

Maximization of the sealing effect of fibrin glue in aortic surgery.

OBJECTIVES: Fibrin glue is used to reinforce anastomosis in aortic surgery. There has not yet been a consensus on how it should be applied optimally. This study aimed to define the optimal condition of applying fibrin glue. METHODS: In experiment 1, we determined the optimal condition for spraying fibrin glue using an expanded polytetrafluoroethylene graft within a needle hole. The length and area of the fibrin cap within the hole were measured. In experiment 2, methods for applying fibrinogen were assessed by comparing brushing and spraying. In experiment 3, swine aorta segments sutured with a Dacron graft were divided into the following three groups: nothing was applied; fibrinogen was sprayed and rubbed using brush. The aorta was clamped and blood was infused from an occlusion catheter inserted into the graft. The pressure at the first appearance of blood leak was recorded. RESULTS: In experiment 1, among the four groups divided by the pressure and distance of spraying, the fibrin cap area in the group with 0.075 MPa and 2-cm spray distance was significantly larger than that in the group with 0.15 MPa and 2 cm (P < 0.01). In experiment 2, the fibrin cap area in the brushing group was significantly larger than that in the spraying group (P < 0.05). In experiment 3, the capacity to resist endoluminal pressure was higher in the brushing and combined spraying group compared with that in the sequential combined spraying group (P < 0.01). CONCLUSIONS: The brush and spray methods showed excellent hemostatic outcomes.

EVI1 expression is associated with aggressive behavior in intrahepatic cholangiocarcinoma.

Ecotropic virus integration site 1 protein homolog (EVI1), a well-known oncogenic transcriptional factor of hematopoietic cells, contributes to pancreatic cancer oncogenicity through increased expression of KRAS. Because EVI1 was upregulated in cholangiocarcinoma by referring The Cancer Genome Atlas, we investigated the importance of EVI1 in intrahepatic cholangiocarcinoma (ICC) which has been regarded as a heterogeneous group of cancers. Immunohistochemical analysis results demonstrated that EVI1 was overexpressed in about half of ICC (53/101, 52.5%). Moreover, all intraductal papillary neoplasms of the bile duct cases expressed EVI1 regardless of histological grading and subtypes such as gastric, intestinal, pancreatobiliary, or oncocytic (20/20, 100%). EVI1-positive ICC showed higher frequencies of aggressive pathological indicators such as periductal infiltrative growth (p = 0.022), hilar invasion (p = 0.041), advanced UICC stage (p = 0.026), major vascular invasion (p = 0.026), and perineural invasion (p = 0.007) than EVI1-negative ICC. Patients with EVI1-positive ICC showed worse overall survival and recurrence-free survival in all resected cases and in curative resected cases. Recently, we proposed type 1/2 (large/small duct types) classification of ICC based on mucin productivity and immunophenotypes (S100P, N-cadherin, and NCAM). Type 1 predominantly consisted of EVI1-positive ICC (33/42 cases, 79%), and the frequency was significantly higher than type 2 (18/55 cases, 32.7%) (p < 0.0001). EVI1-positive ICC was likely to express stomach-specific claudin CLDN18 (correlation coefficient r = 0.55373) and mucin MUC5AC (r = 0.42718). EVI1-positive ICC is an aggressive ICC showing both large-duct and/or gastric phenotypes. Consequently, a transcriptional factor EVI1 is associated with aggressive behavior in ICC and can be a therapeutic target molecule, while EVI1 might be a key molecule for the development of intraductal papillary neoplasms of the bile duct.

Pancreatic Lipomatous Hamartoma: A Hitherto Unrecognized Variant.

Pancreatic masses consisting of lipomatous components clinically include lipoma, liposarcoma, lipomatous pseudohypertrophy of the pancreas, fat-containing neoplasms such as perivascular epithelioid cell tumor, and malignant neoplasm with lipoid degeneration. We present pancreatic lipomatous hamartoma, which has not been reported hitherto. A solid pancreatic mass was detected from a computed tomographic scan check-up in each of 3 cases of Japanese men. Macroscopically, well-demarcated solid lipomatous masses were detected at the uncus, body, and tail of the pancreas, respectively. Microscopically, the masses predominantly consisted of mature adipocytes with no atypia, but contained characteristics components of pancreatic hamartoma, such as small ducts, a well-preserved acinar structure, and/or fibrous stroma. On the basis of the unique features, lack of islets and absence of periductal elastic fibers, these tumors are a distinct variant of pancreatic hamartoma. Furthermore, high-mobility group AT-hook 2 expression in the fibro-adipocytes of this tumor indicated that these cells are an integral component of the pancreatic lipomatous hamartoma. Consequently, the unique tumors described herein are pancreatic lipomatous hamartoma, which must be discriminated from other lipomatous lesions of the pancreas.

Predictors of Heparin Resistance Before Cardiovascular Operations in Adults.

BACKGROUND: Heparin resistance (HR) is often encountered during cardiovascular operations that require cardiopulmonary bypass. Clinical risk factors and the mechanism underlying heparin resistance are yet to be determined. The aim of this study was to elucidate the clinically valid preoperative predictors related to HR. METHODS: The study evaluated 489 patients undergoing cardiovascular operations. Of these, 25 patients presented with HR and received antithrombin III for the initiation of cardiopulmonary bypass with an effective activated coagulation time. The remaining 464 patients, who did not receive antithrombin III, served as controls (NHR). Preoperative patient demographic and laboratory data were analyzed to identify risk factors for HR. RESULTS: The preoperative laboratory data showed platelet count, fibrinogen, D-dimer, creatinine, and C-reactive protein were significantly higher in the HR group than in the NHR group. As expected, the antithrombin III level was significantly lower overall in the HR group (86.0% vs 95.5%, p = 0.009); however, 80% of the patients in the HR group showed normal antithrombin III levels preoperatively. Multivariable logistic regression analysis identified chronic aortic dissection, chronic obstructive pulmonary disease, smoking, and elevated fibrinogen levels as independent predictors for HR. CONCLUSIONS: HR was shown to be associated with preoperative high fibrinogen levels, a smoking habit, and a preoperative diagnosis of chronic, but not acute, aortic dissection, with chronic obstructive pulmonary disease as comorbidity. Administration of antithrombin III resolved HR in all of the affected patients, even when their preoperative antithrombin III level was within the normal limit.

Different desmin peptides are distinctly deposited in cytoplasmic aggregations and cytoplasm of desmin-related cardiomyopathy patients.

Desmin-related cardiomyopathy is a heterogeneous group of myofibrillar myopathies characterized by aggregates of desmin and related proteins in myocytes. It has been debated how the expression and protein structure are altered in the aggregates and other parts of myocytes in patients. To address this question, we investigated the proteome quantification as well as localization in formalin-fixed and paraffin-embedded specimens of the heart of patients by imaging mass spectrometry and liquid chromatography-mass spectrometry analyses. Fifteen tryptic peptide signals were enriched in the desmin-related cardiomyopathy myocardium, twelve of which were identified as desmin peptides with 14.3- to 27.3-fold increase compared to normal hearts. High-intensity signals at m/z 1032.5 and 1002.5, which were desmin peptides 59-70 at the head portion and 213-222 at the 1B domain, were with infrequent colocalization distributed not only in desmin-positive intracytoplasmic aggregates but also in histologically normal cytoplasm, indicating that desmin protein is fragmented and different types of naturally-occurring truncated proteins ectopically assemble throughout the heart of patients. Thus, in addition to conventional histological identification of protein aggregates, specific desmin peptides show a marked difference in quantity and localization in a tissue section of desmin-related cardiomyopathy and differentiate from other cardiomyopathies. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.

Application of low-vacuum scanning electron microscopy for renal biopsy specimens.

Low-vacuum scanning electron microscopy (LV-SEM) has been developed which enables the observation of soft, moist, and electrically insulating materials without any pretreatment unlike conventional scanning electron microscopy, in which samples must be solid, dry and usually electrically conductive. The purpose of this study was to assess the usefulness of LV-SEM for renal biopsy specimens. We analyzed 20 renal biopsy samples obtained for diagnostic purposes. The sections were stained with periodic acid methenamine silver to enhance the contrast, and subsequently examined by LV-SEM. LV-SEM showed a precise and fine structure of the glomerulus in both formalin fixed paraffin and glutaraldehyde-osmium tetroxide-fixed epoxy resin sections up to 10,000-fold magnification. The spike formation on the basement membrane was clearly observed in the membranous nephropathy samples. Similarly to transmission electron microscopy, electron dense deposits were observed in the epoxy resin sections of the IgA nephropathy and membranous nephropathy samples. LV-SEM could accurately show various glomerular lesions at high magnification after a simple and rapid processing of the samples. We consider that this is a novel and useful diagnostic tool for renal pathologies.

[Ebstein's anomaly in an adult].

A 56-year-old female who had been diagnosed with Ebstein's anomaly was admitted with cyanosis and congestive heart failure. The echocardiogram showed severe tricuspid valve incompetence, displacement of the tricuspid valve and dilatation of the atrialized portion of the right ventricle. Atrial fibrillation was detected in the electrocardiogram. She underwent tricuspid valve replacement and right atrial maze procedure. She is released from congestive heart failure and remains in sinus rhythm 48 months after the operation.

Construction of disarmed Ti plasmids transferable between Escherichia coli and Agrobacterium species.

Agrobacterium-mediated plant transformation has been used widely, but there are plants that are recalcitrant to this type of transformation. This transformation method uses bacterial strains harboring a modified tumor-inducing (Ti) plasmid that lacks the transfer DNA (T-DNA) region (disarmed Ti plasmid). It is desirable to develop strains that can broaden the host range. A large number of Agrobacterium strains have not been tested yet to determine whether they can be used in transformation. In order to improve the disarming method and to obtain strains disarmed and ready for the plant transformation test, we developed a simple scheme to make certain Ti plasmids disarmed and simultaneously maintainable in Escherichia coli and mobilizable between E. coli and Agrobacterium. To establish the scheme in nopaline-type Ti plasmids, a neighboring segment to the left of the left border sequence, a neighboring segment to the right of the right border sequence of pTi-SAKURA, a cassette harboring the pSC101 replication gene between these two segments, the broad-host-range IncP-type oriT, and the gentamicin resistance gene were inserted into a suicide-type sacB-containing vector. Replacement of T-DNA with the cassette in pTiC58 and pTi-SAKURA occurred at a high frequency and with high accuracy when the tool plasmid was used. We confirmed that there was stable maintenance of the modified Ti plasmids in E. coli strain S17-1lambdapir and conjugal transfer from E. coli to Ti-less Agrobacterium strains and that the reconstituted Agrobacterium strains were competent to transfer DNA into plant cells. As the modified plasmid delivery system was simple and efficient, conversion of strains to the disarmed type was easy and should be applicable in studies to screen for useful strains.

Bioabsorbable gelatin sheets latticed with polyglycolic acid can eliminate pericardial adhesion.

BACKGROUND: As an extension of our previous studies on bioabsorbable pericardial substitutes, we have created a new form of gelatin sheets latticed with bioabsorbable polyglycolic acid (PGA). This study was undertaken to evaluate the biomechanical property of the sheet and the preventive effect on pericardial adhesions after pericardial replacement in a canine model before its clinical applications. METHODS: The mechanical property was assessed by measuring tension of suture pull-out at first break test. Fifteen dogs underwent partial pericardial replacement with the bioabsorbable sheets through a left thoracotomy. Macroscopic assessment for severity of adhesions and microscopic evaluation for histologic changes were made at 2, 4, 12, and 24 weeks postoperatively. RESULTS: The latticed sheets exhibited tenfold higher tension of disruption at the suturing margin compared to our previously developed gelatin sheets (619 +/- 141 versus 62 +/- 7 gf, p < 0.001), and demonstrated equivalent strength to that of clinically available expanded polytetrafluoroethylene membrane. During rethoracotomy, adhesions between the epicardium and the pericardial substitutes were moderate at the 4-week interval and resolved completely after 12 weeks postoperatively. Inflammatory reaction scores graded into 4 scales on histologic assessment were 2 +/- 0.0, 1.6 +/- 0.6, and 0.3 +/- 0.5 at 4, 12, and 24 weeks, respectively. Inflammatory reaction significantly decreased from the 4-week interval to the 24-week interval after the pericardial replacement (p < 0.05). CONCLUSIONS: The bioabsorbable gelatin sheets latticed with PGA gained improved mechanical properties compared with the previously reported gelatin sheets without impairing its bioabsorbability. The bioabsorbable sheet could eliminate pericardial adhesions after being replaced with regenerated tissue.

Closure of the pericardium using synthetic bioabsorbable polymers.

BACKGROUND: Pericardial substitutes are known to ensure safer resternotomy at reoperation. A synthetic sheet made from expanded-polytetrafluoroethylene (e-PTFE) has been most commonly used as a pericardial substitute. The e-PTFE sheet, however, can induce severe inflammatory reaction and diffuse fibrosis. This study was designed to investigate the absorption rate and tissue reaction associated with two absorbable pericardial substitutes: a gelatin sheet and L-lactic acid-epsilon-caprolactone copolymer (L-C copolymer). In addition, e-PTFE sheet and autologous pericardium were used as controls. METHODS: Sixty dogs were divided into four groups of 15. In group A, a 3 x 3 cm segment of pericardium was excised, and the autologous pericardium was resutured. In group B, the pericardial defect was replaced with gelatin sheet. In group C, the defect was replaced with L-C copolymer sheet. In group D, the defect was replaced with e-PTFE sheet. For each group, the implanted membranes were retrieved at 2 weeks (n = 1), 4 weeks (n = 3), 12 weeks (n = 5), and 24 weeks (n = 6) after implantation. RESULTS: The e-PTFE sheet produced severe adhesions to the heart and pleura and a more prominent inflammatory reaction, as compared with the gelatin sheet. The absorbable pericardial substitutes were completely absorbed by 24 weeks after implantation, and were replaced with fibrous membrane. CONCLUSIONS: Gelatin sheet may involve less adhesion and a reduced inflammatory reaction compared with e-PTFE.

Axillary artery cannulation improves operative results for acute type a aortic dissection.

BACKGROUND: This study was undertaken to identify preoperative and postoperative predictors of hospital death of patients with acute type A aortic dissection. METHODS: Between May 1,1992, and July 31, 2004, 106 consecutive patients (59 male and 47 female, mean age 62.2 +/- 12.1 years) with acute type A aortic dissection underwent surgery with open technique and cerebral protection by antegrade selective cerebral perfusion. The external iliac artery or femoral artery alone was used for arterial cannulation in 37 patients; however, the right axillary artery was cannulated in 69 patients. Univariate analysis of potential risk factors was performed to identify risk factors for hospital death and was followed by multivariate analysis by a stepwise logistic regression model to identify independent risk factors. RESULTS: Sixteen patients died postoperatively, and the overall hospital mortality rate was 15.1%. Univariate analysis revealed shock (p = 0.020), visceral ischemia (p = 0.007), root replacement (p = 0.041), and absence of axillary artery perfusion (p = 0.003) as significant risk factors for hospital death. Multivariate analysis revealed visceral ischemia (p = 0.0028, odds ratio 18.4) and absence of axillary artery perfusion (p = 0.0014, odds ratio 8.2) as independent preoperative and intraoperative predictors of hospital death. CONCLUSIONS: Achievement of greater success in the surgical treatment of acute type A dissection will require axillary artery cannulation and measures to prevent visceral malperfusion.

A successful management of concomitant renovascular hypertension and symptomatic subclavian steal syndrome due to Takayasu's arteritis using balloon angioplasty and axillo-axillary bypass grafting.

We present a case of Takayasu's arteritis with severe renovascular hypertension and symptomatic subclavian steal syndrome. A 60-year-old woman underwent successful percutaneous balloon renal angioplasty and axillo-axillary bypass grafting. The role of hybrid therapy, angioplasty and extra-anatomical bypass grafting for revascularization of symptomatic ischemia in this disease is reviewed. (Ann Thorac Cardiovasc Surg 2003: 9; 334-6)

Acute mitral regurgitation due to total rupture in the anterior papillary muscle after acute myocardial infarction successfully treated by emergency surgery.

A 68-year-old female was admitted for sudden onset of chest pain. She received a successful percutaneus coronary intervension for total occlusion in the diagonal artery, but continued to develop progressive heart failure. A chest X-ray showed right pulmonary edema without cardiomegaly, and an echocardiogram revealed massive mitral regurgitation with prolapse in the anterior mitral leaflet due to a rupture in the papillary muscle. An emergency operation was conducted using routine cardiopulmonary bypass. There was complete rupture in the anterior papillary muscle. Mitral valve replacement with posterior mitral leaflet preservation was performed using a size 25 mm Carbomedics prosthetic valve. The postoperative course was uneventful, and she was discharged on postoperative day 29 in New York Heart Association class I. Postoperative pathological findings showed necrosis in the papillary muscle with inflammatory changes. Early diagnosis, prompt medical stabilization, and aggressive surgical intervention are essential to save such a group of patient.