Early clinical evaluation of the Cosgrove-Edwards prosthetic heart valve ring

 We discuss the usefulness of the Cosgrove-Edwards ring from our early clinical results from 25 rings in 24 patients who underwent mitral annuloplasty (MAP) or tricuspid annuloplasty (TAP) between June 1999 and December 2000. In the MAP group, the posterior mitral annulus between the anterior and posterior fibrous trigones was reinforced with the prosthetic ring. In the TAP group, the annuli of the anterior and posterior leaflets were splinted with the ring. The prosthetic ring was attached by pledgeted U-sutures. Cardiologists performed echocardiography pre- and postoperatively. Thirteen of the 14 in the MAP group showed mitral valve regurgitation of grade 0 or I. Six of the 11 in the TAP group showed tricuspid regurgitation of grade 0 or I, and 5 patients with regurgitation equal to or greater than grade II who remained in atrial fibrillation postoperatively recovered without further clinical symptoms. No patient has required reoperation during a follow-up period of up to 2 years. Cosgrove-Edwards ring-related complications, such as valve stenosis, ring detachment, and arrhythmia, have been not recognized in these patients. In conclusion, for mitral and tricuspid annuloplasty, the Cosgrove-Edwards prosthetic ring showed excellent early clinical results, particularly in patients maintained in sinus rhythm. Received: November 5, 2001 / Accepted: May 30, 2002 Correspondence to:Y. Misawa     

Blockade of Rho/Rho-associated coiled coil-forming kinase signaling can prevent progression of hepatocellular carcinoma in matrix metalloproteinase-dependent manner

Aim:  There is growing evidence that the Rho/Rho-associated coiled coil-forming kinase (ROCK) signaling pathway is upregulated in tumors and plays a key role in cancer invasion and metastasis. Our aim was to test the anticancer effects of Rho/ROCK inhibitor, Y-27632, including possible mechanisms in a highly-metastasizing hepatocellular carcinoma (HCC) mouse model on its secretion of matrix metalloproteinase (MMP) and tumor progression.
Methods:  Following orthotopic implantation of CBO140C12 HCC tumor fragments into the liver of mice, the mice were randomly assigned to a Y-27632-treated group or control group. After treatment for 4 weeks, specimens were obtained to evaluate tumor size, metastases, and immunohistochemical findings. In vitro , we examined the effects of Y-27632 and RhoC siRNA on MMP-2 and -9 expressions, invasiveness, and apoptosis in cultured tumor cells.
Results:  Both RhoA and RhoC were upregulated in HCC-bearing livers, and Y-27632 significantly inhibited not only tumor growth and intrahepatic metastasis ( P  < 0.05), but also tumoral MMP-9 expression. Moreover, Y-27632 treatment resulted in large necrotic areas in tumors. In vitro , Y-27632 and RhoC siRNA reduced MMP-2 and -9 expressions, as well as the chemotactic migration of tumor cells dose-dependently, and increased apoptosis eight times.
Conclusion:  Y-27632 suppresses progression and limits the intrahepatic metastasis of established HCC. This could be linked to the decreased MMP expression and induction of apoptosis in tumor cells. Rho signaling may prove to be a productive target in anticancer therapy.     

Organ Correlation in IgG4-Related Diseases

IgG4-related disease (IgG4-RD) is a potentially multiorgan disorder. In this study, clinical and serological features from 132 IgG4-RD patients were compared about organ correlations. Underlying pathologies comprised autoimmune pancreatitis (AIP) in 85 cases, IgG4-related sclerosing cholangitis (IgG4-SC) in 12, IgG4-related sialadenitis (IgG4-SIA) in 56, IgG4-related dacryoadenitis (IgG4-DAC) in 38, IgG4-related lymphadenopathy (IgG4-LYM) in 20, IgG4-related retroperitoneal fibrosis (IgG4-RF) in 19, IgG4-related kidney disease (IgG4-KD) in 6, IgG4-related pseudotumor (IgG4-PT) in 3. Sixty-five patients (49%) had multiple IgG4-RD (two affected organs in 36 patients, three in 19, four in 8, five in 1, and six in 1). Serum IgG4 levels were significantly higher with multiple lesions than with a single lesion (P<0.001). The proportion of association with other IgG4-RD was 42% in AIP, the lowest of all IgG4-RDs. Serum IgG4 level was lower in AIP than in other IgG4-RDs. Frequently associated IgG4-RDs were SIA (25%) and DAC (12%) for AIP; AIP (75%) for IgG4-SC; DAC (57%), AIP (38%) and LYM (27%) for IgG4-SIA; AIP (26%) and LYM (26%) for IgG4-DAC; SIA (75%), DAC (50%) and AIP (45%) for IgG4-LYM; SIA (58%), AIP (42%) and LYM (32%) for IgG4-RF; AIP (100%) and SIA (67%) for IgG4-KID; and DAC (67%) and SIA (67%) for IgG4-PT. Most associated IgG4-RD lesions were diagnosed simultaneously, but IgG4-SIA and IgG4-DAC were sometimes identified before other lesions. About half of IgG4-RD patients had multiple IgG4-RD lesions, and some associations were seen between specific organs.

Graphical Abstract

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A new thrombolytic agent,monteplase, is independent of the plasminogen activator inhibitor in patients with acute myocardial infarction: initial results of the COmbining Monteplase with Angioplasty (COMA) trial

Background Both thrombolytic therapy and coronary angioplasty have been inconsistent together for primary acute myocardial infarction (AMI) therapy, because conventional thrombolytic agents accelerate plasminogen activator inhibitor-1 (PAI-1) activity. However, combining newly developed mutant tissue-type plasminogen activators with coronary angioplasty should be reconsidered. Methods This study was designed to investigate clinical usefulness of such an agent, monteplase, for treatment of AMI in light of PAI-1 kinetics. One hundred fifty-four consecutive patients with AMI were randomly assigned to receive direct coronary angioplasty (Group I) or coronary angioplasty after pretreatment with intravenous monteplase (Group II). In 90 of these patients, total PAI-1 antigen levels were serially measured. Results Baseline PAI-1 levels at admission were higher in patients with occluded infarct-related arteries than in patients with patent arteries in Group I (39 ± 4 vs 20 ± 2 ng/mL, P < .01) and in Group II (36 ± 3 vs 27 ± 2 ng/mL, P < .05). In the high PAI-1 level subgroup (≥27 ng/mL, n = 53), Group II showed a higher patency rate than Group I (56 vs 18%, P < .01). Multiple logistic regression analysis indicated that patency could be predicted by the PAI-1 level in Group I (Wald χ²= 3.94, P = .02, odds ratio 0.924, 95% CI 0.855-0.999), but not in Group II. Serial change patterns in the PAI-1 level were identical in Group I and Group II. Conclusion Because monteplase can be used independently of PAI-1 kinetics, a combination of monteplase administration at a community hospital with prompt transfer to a tertiary center for coronary intervention may be a powerful strategy for AMI. (Am Heart J 2002;144:e5.)     

Possibility of slow-growing variants in pancreatic adenocarcinoma

Four patients with advanced pancreatic adenocarcinoma suggesting slow-growing tumors are reported on. Tumors in 2 of the 4 were far-advanced, but both survived for over 3 years after treatment. One demonstrated 165 days of serum CA 19-9 level doubling time (T2CA 19-9), while the other demonstrated 135 days of DUPAN II level doubling time. Late tumor recurrence was observed in the remaining 2 patients who survived over 8 years after surgery, demonstrating long-term T2CA 19-9. A long-term T2CA 19-9 of 141 days was correlated with slow tumor growth in computed tomography (CT) scans in 1 patient, who survived 2.5 years after evidence of recurrent tumor without supplementary therapy. These observations, which suggest slow-growing variants, have not been reported in the literature on pancreatic adenocarcinoma. A significant difference was also seen in tumor-marker doubling time among 6 patients who survived over 3 years and 26 patients who did not (p = 0.02). Thus, the doubling time may characterize certain tumors biologically in a way that is useful in practice for predicting disease outcome.     

Annular pancreas associated with carcinoma in the dorsal part of pancreas divisum

Summary A carcinoma in the dorsal part of the pancreas divisum with an annular pancreas in the anterior part is reported. A 79-yr-old female was admitted in our hospital complaining of epigastralgia. Computed tomography (CT) and ultrasound (US) showed an irregular mass in the pancreatic body. A pancreatogram obtained through the major duodenal papilla demonstrated only the ventral pancreatic duct that encircled the duodenum. Contrast medium injected from the minor duodenal papilla showed Santorini’s duct obstruction at the neck portion of the pancreas without communication with the ventral pancreatic duct. The patient died with liver metastases. Autopsy confirmed annular pancreas and a 6-cm tumor in the pancreatic body extending to the pancreatic head and pancreas divisum. Pancreatic carcinoma; histologically a moderately differentiated adenocarcinoma; originated from the dorsal part of pancreas divisum. To our knowledge this is the first report of pancreatic carcinoma associated with annular pancreas coexistent with pancreas divisum.     

Diagnostic criteria for autoimmune pancreatitis in Japan

Autoimmune pancreatitis （AIP） is a particular type of pancreatitis of presumed autoimmune etiology. Currently, AIP should be diagnosed based on combination of clinical, serological, morphological, and histopathological features. When diagnosing AIP, it is most important to differentiate it from pancreatic cancer. Diagnostic criteria for AIP, proposed by the Japan Pancreas Society in 2002 first in the world, were revised in 2006. The criteria are based on the minimum consensus of AIP and aim to avoid misdiagnosing pancreatic cancer as far as possible, but not for screening AIR The criteria consist of the following radiological, serological, and histopathological items： （1） radiological imaging showing narrowing of the main pancreatic duct and enlargement of the pancreas, which are characteristic of the disease; （2） laboratory data showing abnormally elevated levels of serum y-globulin, IgG or IgG4, or the presence of autoantibodies; （3） histopathological examination of the pancreas demonstrating marked fibrosis and prominent infiltration of lymphocytes and plasma cells, which is called lymphoplasmacytic sclerosing pancreatitis （LPSP）. For a diagnosis of AIP, criterion 1 must be present, together with criterion 2 and/ or criterion 3. However, it is necessary to exclude malignant diseases such as pancreatic or biliary cancer.     

Origin of the long common channel based on pancreatographic findings in pancreaticobiliary maljunction

BACKGROUND AND AIMS: The origin of a long common channel in pancreaticobiliary maljunction was suggested to be the ventral pancreatic duct. Pathogenesis of long common channels was investigated by anatomically analysing the arrangement of pancreatic ducts in pancreaticobiliary maljunction. MATERIALS AND METHODS: Cholangiopancreatography was performed for 66 cases of pancreaticobiliary maljunction and 200 controls. The accessory pancreatic duct was classified according to course and shape. In cases with long- or short-type accessory pancreatic duct, lengths of the main pancreatic duct from orifice to first inferior branch and junction with the accessory pancreatic duct, and the common channel were measured. RESULTS: Lengths of the main pancreatic duct from orifice to first inferior branch or junction with the accessory pancreatic duct were significantly longer in cases of pancreaticobiliary maljunction cases with the long- or short-type accessory pancreatic duct than in controls (p<0.01). Lengths of the main pancreatic duct from first inferior branch to junction with the accessory pancreatic duct were roughly equivalent in pancreaticobiliary maljunction and controls. CONCLUSIONS: Long common channels in pancreaticobiliary maljunction might be formed embryologically with adhesion of the right ventral pancreatic duct and the terminal portion of the bile duct.