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We report seven large B cell lymphoma patients showing the involvement of tumor cells with cyclin D3 (CCND3) expression in bone marrow (BM) at the initial diagnosis. All patients presented with B symptoms, splenomegaly, and anemia/thrombocytopenia lacking hemophagocytosis in the BM. Five of the seven patients had suffered from immunological diseases or cancers. The tumor cells were divided into those with a lymphoplasmacytoid or blastoid appearance. Six cases were confirmed to express CD5 antigen on tumor cells. Three cases presented a chromosomal translocation between CCND3 and the immunoglobulin heavy chain (IGH) loci, t(6;14)(p21;q32). Three and two cases showed unmutated and mutated sequences of the variable region of IGH (VH), respectively, and one case showed deletion of an entire segment of VH. Two cases with t(6;14)(p21;q32) showed an unmutated VH sequence and chromosomal translocation within the switch region of IGH. Further studies are required to determine whether CCND3 expression is associated with a unique subset of diffuse large B cell lymphoma.

We report a follicular lymphoma (FL) case presenting the coexistence of two tumor cell subpopulations in lymph node (LN) and bone marrow (BM), which exhibited an inverse pattern of immunoglobulin light (IgL) chain gene rearrangement and expression: Igkappa-lambda+ in LN and Igkappa+lambda- in BM. These tumor clones shared an identical BCL2-IgH recombination, accompanying t(14;18)(q32;q21) translocation, and an identical variable, diversity and joining segments joining with clone-specific VH somatic hypermutations on the untranslocated IgH allele. Our study provides further evidence that FL clones, originating from common progenitor cells, can be developed independently at different sites and with different IgL expression after immune selection.

It remains unclear how cardioplegic arrest affects surgical results after coronary artery bypass grafting surgery (CABG). This study compares early outcomes after on-pump beating-heart CABG and conventional CABG.From 2002 to 2005, 114 patients underwent on-pump beating-heart CABG. Multivariate logistic regression revealed five characteristics according to which technique is liable to be used: history of cerebral infarction, urgent or emergent operation, lower ejection fraction, preoperative creatine kinase, and lower number of diseased vessels. The early clinical outcome for these patients was compared against 114 conventional CABG patients, matched using a propensity score constructed with these five significant variables and with two nonsignificant variables: history of diabetes mellitus and hypertension.On-pump beating-heart CABG significantly reduced the duration of operation and cardiopulmonary bypass, total blood loss, and peak creatine kinase (p0.05). The number of patients requiring additional intra-aortic balloon pump support was significantly lower in the on-pump beating-heart CABG group (2 versus 13, p0.01). No patients required percutaneous cardiopulmonary support after on-pump beating-heart CABG, whereas 4 patients needed it after conventional CABG. Complete revascularization was significantly lower (42.1% versus 77.2%, p0.0001), but in-hospital mortality was less in the on-pump beating-heart CABG group (2.6% versus 9.6%, p0.05). No significant difference was found in morbidity including stroke, renal failure, mediastinitis, and prolonged ventilation.On-pump beating-heart CABG can be performed safely, including on high-risk patients. Use of cardiopulmonary bypass and the elimination of cardioplegic arrest may be of most benefit to hemodynamically unstable patients.

Myelodysplastic syndromes (MDS), especially refractory anemia (RA) are very heterogeneous diseases regarding their morphological, biological and clinical features. One important clinical problem is the difficulty of diagnosis. Soluble transferrin receptors (sTfRs) reflect the erythropoietic activity in the bone marrow (BM). To establish whether determination of serum sTfR could be useful for the differential diagnosis between RA and aplastic anemia (AA), we measured the serum sTfR concentrations, BM cellularity and BM erythroblast percentages in 14 untreated AA and 7 untreated RA patients. The serum sTfR levels of the RA patients (820.1 ± 402.8 ng/ml) were significantly higher than those of the AA patients (491.1 ± 195.2 ng/ml; p = 0.0207). However, the serum sTfR values of RA and AA patients also overlapped. A new index, the ‘sTfR-E index’ [the ratio of serum sTfR level (ng/ml) to BM cellularity (%) × BM erythroblasts (%)] is proposed, which is expected to reflect the number of transferrin receptors (TfR) on the cell membrane per BM erythroblast. The sTfR-E index values of the 7 RA patients (0.395 ± 0.234) were significantly lower than those of the 14 AA patients (2.669 ± 1.633; p = 0.0003). The sTfR-E index values of AA and RA patients overlapped only marginally. In conclusion, the sTfR-E index may be a useful new diagnostic tool to distinguish between AA and RA patients.

Mitoxantrone, etoposide and prednisone (MEP)-based regimens using granulocyte colony-stimulating factor (G-CSF) were designed for relapsed and CHOP-resistant diffuse large B-cell lymphomas in a single institution, and the therapeutic effects and adverse reactions were studied. In a total of 49 patients, the MEP regimen had a 41% (9/22) overall response rate compared with 48% (13/27) for the MEP plus carboplatin (C-MEP) regimen (Chi-squared test, P=0.602). Among 38 CHOP-resistant patients, however, the overall response rate to C-MEP [42% (10/24)] was significantly superior compared with MEP [7% (1/14)] (P=0.023), and the overall survival to C-MEP was superior compared with MEP (P=0.088). Taken together, our results, although non-randomized, suggest that a combination of MEP with carboplatin is better than MEP alone in CHOP-resistant diffuse large B-cell lymphomas.

Management of the small aortic root is a significant problem for the surgeon with regard to operative technique and selection of the prosthesis. We report on four adults with a small aortic root who underwent aortic valve replacement with a 16-mm CarboMedics bileaflet valve. All patients now lead normal lives. Postoperative Doppler measurements demonstrated an acceptable transprosthetic gradient.

Cardiopulmonary support (CPS) requires durability of the oxygenator. The life span of the oxygenator is affected by various clinical factors, including patient condition, perfusion condition, and equipment usage. Predictors for the durability of oxygenators were evaluated clinically in this study. Thirty-two patients, who had undergone CPS during the last 3 years in our institute were assigned to this study. Fifty oxygenators had been used (Capiox SX in 19, CB Maxima in 23, and AL-6000 in 8). Significant predictors for the durability of oxygenators were evaluated by nonparametric survival analysis and proportional hazards regression analysis. Univariate regression analysis revealed 6 significant predictors for the life span of oxygenators. These were the oxygenator type, type of centrifugal pump, acidosis with blood pH less than 7.35, base excess less than -5, blood glutamic-oxaloacetic transaminase (GOT) levels greater than 1,000 IU, and blood lactate dehydrogenase (LDH) levels greater than 3,000 IU. After multivariate analysis, there remained only 2 significant predictors. An oxygenator used with a noncoated CPS system (Capiox SX with Capiox EBS) proved to have a significantly shorter life span than one used with a heparin-coated system (CB Maxima or AL-6000 with CB BP-80) (hazards ratio, 3.588, p = 0.0065). Patient conditions, which revealed acidosis with less than -5 of base excess, significantly shortened the life of the oxygenator (hazards ratio, 3.595, p = 0.0188).

Background. Nafamostat mesilate (FUT-175) is a synthetic serine protease inhibitor that inactivates coagulation, fibrinolysis, and platelet aggregation. Nafamostat mesilate may suppress the blood-foreign surface reaction similar to biocompatible materials by blocking factor XIIa. Methods. We performed an in vitro study of cardiopulmonary bypass (CPB) with fresh human blood among the following three groups: standard CPB sets (C), biocompatible CPB sets (B), and standard CPB sets with FUT-175 (10 mg/L) (F). A clinical study using these same CPB groups also was performed in 45 patients undergoing aortocoronary bypass operations (15 patients each). We injected FUT-175 at 40 mg/h during CPB. Results. In the in vitro study, both groups B and F showed significantly lower levels of coagulation factors, thrombin-antithrombin III complex, fibrinopeptide A, β -thromboglobulin, complement C3a, granulocyte elastase, and free hemoglobin than group C at the conclusion of the study. Thrombin-antithrombin III complex and free hemoglobin in group F also were lower than in group B. The platelet count remained at a higher level in group F than in the other groups. Separation of bradykinin was suppressed most significantly in group F. In the clinical study, group F also showed significantly lower levels of α 2-plasmin inhibitor plasmin complex and C3a than both groups C and B. There were minimal levels of free hemoglobin in group F. Conclusions. Nafamostat mesilate may contribute major beneficial effects toward conservation of blood during CPB and prevention of coagulopathy after CPB.

Adverse effects of cardiopulmonary bypass on cancer prognosis are expected but have not been confirmed. Seventy-four cancer patients who underwent cardiac surgery before cancer therapy were followed up for 42 ± 37 months; 45 had cardiac surgery with cardiopulmonary bypass. There was no significant difference in cancer recurrence (40.0%) and deaths (26.7%) among patients who had cardiopulmonary bypass and those who underwent off-pump cardiac surgery (27.6% and 24.1%). There were no significant differences in freedom from cancer-related death at 2 and 5 years after cardiac surgery (78.4% and 68.5%) in the cardiopulmonary bypass group compared to the 29 off-pump group (81.8% and 58.3%). Despite some limitations, this study detected no significant adverse effects of cardiopulmonary bypass on cancer prognosis. Although these results do not verify the safety of cardiopulmonary bypass from an oncologic aspect, they suggest it can be applied in cancer patients who require cardiac surgery.

The BCL6 gene is frequently disrupted at its 5′ noncoding region by 3q27 chromosomal translocations in B-cell lymphoma. As a result of translocation, BCL6 is juxtaposed to reciprocal partners, such as the immunoglobulin ( Ig ) gene family. Besides the Ig loci, multiple non- Ig partners of the BCL6 translocation have been reported. Here we describe the identification of the GAS5 (growth arrest-specific transcript 5) gene as a novel partner of the BCL6 in a patient with diffuse large B-cell lymphoma, harboring the t(1;3)(q25;q27). In this case, the chromosome 1 breakpoint was located within the intronic small nucleolar RNA (snoRNA) sequence of GAS5 and the chromosome 3 breakpoint at 4 kb upstream of BCL6 exon 1a. As the result of chromosomal translocation, the GAS5–BCL 6 chimeric transcripts were expressed, in which the 5′-terminal oligopyrimidine (5′TOP) sequence of GAS5 was fused to the whole coding sequence of BCL6 . The GAS5 gene on chromosome 1q25 is the second BCL6 partner, to the SNHG5 on 6q15, which is classified as a non-protein-coding multiple snoRNA host and 5′-TOP class gene.

A 62-year-old woman was admitted to our hospital because of gastric mucosal bleeding. Gastroendoscopy revealed a gastric tumor which was diagnosed from the biopsied specimen as diffuse large B-cell lymphoma (DLBCL). Lymphoma cells had infiltrated the bone marrow showed morphological features resembling Burkitt lymphoma (BL). Nearly 100% of the cells in the bone marrow were positive for MIB-1 immunostaining. The chromosomal study was normal. Surface marker analysis disclosed that the cells were positive for CD10, CD19, CD20 and CD25. As lymphoma cells had infiltrated the central nervous system, combined chemotherapy was performed accompanied with intrathecal administration of anticancer drugs. Although transient improvement was observed, the patient died of the advanced disease three months after admission. As we have shown here, there are some cases of DLBCL with immunohistochemical features resembling BL. Further consideration about the appropriate chemotherapy program for this type of disease might be necessary.

A 61-year-old man with primary macroglobulinemia (PMG) had been followed without any treatment as he had no apparent manifestations. After 1 year and 3 months, he was admitted to our hospital with a fever. No signs or symptoms of infection and no progressive increase of serum IgM levels was observed. Non-Hodgkin's lymphoma was not additionally found. Fever without infection, elevated serum LDH level and further enlargement of the spleen compelled us to diagnose his condition as deterioration of the PMG. An immediate fall in his temperature and serum IgM levels was observed after CHOP therapy. Effective therapy must be discussed in the deterioration of this type of disease.

A 60-year-old female visited our hospital in May 2001 because of systemic lymphadenopathy. Her white blood cell count was 25,510/microliters with 93% of lymphocytes. Bone marrow aspiration revealed that 86% of nucleated cells were lymphocytes. Lymphocytes in the peripheral blood and bone marrow were positive for CD 5, 19, 20, and sIgx and negative for CD 23. FISH analysis detected the chimeric bcl 1/IgH fusion gene. Immunohistochemistry of a biopsied lymph node revealed that lymphoma cells were positive for cyclin D 1. Mantle cell lymphoma (MCL) was diagnosed at clinical stage IV A. Although a partial remission was obtained after CHOP plus rituximab therapy, the patient's disease recurred in March 2002 and she died in spite of salvage therapy including rituximab. Immunohistochemistry of the bone marrow cells after salvage rituximab therapy revealed that lymphoma cells were still positive for CD 5 and cyclin D 1, but negative for CD 20 and sIgx. We could not exactly determine how frequently CD 20 expression becomes negative in B-cell lymphomas after treatment with rituximab. We found only two reported cases that suggested rituximab down-regulated CD 20 expression in MCL. We herein describe a case of MCL with very notable clinical features.

The aim of this study was to evaluate the cause and treatment of atrial flutter after coronary artery bypass grafting (CABG).Between July 1999 and July 2000, 96 CABGs were performed at the Cardiovascular Center of Aichi Prefectural Owari Hospital. We compared two groups of patients: those with atrial flutter after CABG (group A) and those without atrial flutter (group B).We treated the atrial flutter group with medication, electrical defibrillation, and overdrive pacing. Six of these cases later required radiofrequency catheter ablation (RFCA). These were all with common-type atrial flutter, treated by RFCA for the posterior isthmus, without difficulty. The frequency of direct cannulation to the coronary sinus for retrograde cardioplegia was significantly higher in group A.Incidence of atrial flutter after CABG was influenced by surgical damage arising from direct cannulation to the coronary sinus for retrograde cardioplegia. Preoperative viability of the myocardium (in addition to good myocardial protection during surgery) also seems to be associated with an increased likelihood of postoperative atrial flutter.

In our previous study, approximately 60% of aplastic anemia (AA) and refractory anemia (RA) patients treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human erythropoietin (rhEpo) showed a multilineage response. In this study, we analyzed the long-term follow-up of the multilineage responders (multi-R). In the follow-up analysis of 11 multi-R (6 AA and 5 RA), 10 patients (5 AA and 5 RA) were evaluable. The range of time from the start of treatment to the final contact was 50 to 125 months. Analysis of survival times revealed a significant difference between multi-R and non-multi-R among AA patients given this treatment (P = .016). One AA and 1 RA patient among the multi-R developed acute leukemia. Of 7 living multi-R, 3 AA and 2 RA patients did not need transfusion at final contact. Four of them maintained the target hemoglobin concentration of more than 11 g/dL for quality-of-life benefit. The findings suggested that this result is an important advantage of this treatment.

A 56-year-old man admitted with dyspnea had undergone aortic valve replacement using a Starr-Edwards ball valve to treat aortic regurgitation 28 years earlier. Chest radiography showed moderate cardiomegaly, moderate pulmonary edema, and mild pleural effusion. Echocardiographic examination showed severe mitral regurgitation. The mitral valve was replaced using a St. Jude Medical prosthesis, and the Starr-Edwards aortic valve was replaced using a CarboMedics prosthetic valve. The cloth covering on the Starr-Edwards valve had worn away and pannus had formed. The patient's postoperative course was uneventful, and he was discharged on postoperative day 35.

Before and after therapy, serum thymidine kinase (TK) and soluble interleukin-2 receptor (sIL-2R) were serially determined in 28 patients with malignant lymphoma (ML). In 15 patients achieving and maintaining complete remission (CR) for more than 2 years, serum TK and sIL-2R were unchanged or decreased gradually. In contrast, logarithmic linear increases of TK and sIL-2R were observed in 13 relapsed patients. The increments of the serum markers occurred more than 10 months before the relapse. A significant positive correlation between the slope of the line for TK and that for sIL-2R was noted. The doubling time for TK estimated from the slope also showed a positive correlation with that for sIL-2R. Taken together, serum TK and sIL-2R were shown to be quite sensitive and interrelated serum markers for the recurrence of ML. Slopes of logarithmic linear increase, which are proper and specific for the individual patients, are inversely correlated with the doubling time and reflect proliferation of ML. We conclude that serum TK and sIL-2R are better predictors of relapse than LDH and the international prognostic index (IPI).

Background: Nisoldipine, a calcium antagonist, was assessed for myocardial protection and the prevention of reperfusion injury in patients undergoing CABG.Methods: Of the 34 subjects undergoing CABG in this study, 20 were given nisoldipine orally at 10 mg/day for 2 weeks before surgery (N group) and the other 14 untreated controls (C group). Myocardial protection was conducted via antegrade cold blood cardioplegia at 20-minute intervals.Results: Myocardial blood flow was significantly higher in the N group (67.8±21.8 ml/100 g vs. 47.2±14.4 ml/100 g, p < 0.05) after cardiopulmonary bypass. Serum interleukin-6 levels were significantly lower in the N group 1 hour after reperfusion (116±58 vs. 409±362 pg/ml, p < 0.05), as were serum lactate dehydrogenase levels immediately after surgery (888±268 vs. 1350±486 IU/L, p < 0.05). The N Group showed a better left ventricle stroke work index 6 hours after surgery (43±8 vs. 36±9 g·m/m2). Dopamine dosage in the N group on postoperative day 1 was lower than in controls (5.3±1.9 vs. 3.0±2.4 μg/kg/min). Conclusions: Preoperative nisoldipine treatment increased blood flow in the postischemic myocardium and prevented myocardial damage and reperfusion injury to some extent.

Cannulation of the ascending aorta is the recognized method to achieve arterial return during cardiopulmonary bypass. Mediastinal infection after cardiac surgery can cause disruption at the point of insertion, and give rise to a pseudoaneurysm in the ascending aorta. Although rare, a pseudoaneurysm can occur without clear evidence of infection. Here we report two cases that received aortic valve replacement and that developed ascending aortic aneurysms after surgery. Based on our clinical findings, these aneurysms were related to the arterial cannulation into the aorta and not to any infection.

Currently, poststernotomy mediastinitis frequently is being treated by debridement and immediate closure with omental drainage. This method is useful, but subcutaneous infection occasionally occurs. Divided omental transfer to the presternal space may be helpful in preventing this complication.

We report herein the unusual case of a patient in whom postoperative angiography following coronary artery bypass grafting (CABG) revealed a lateral origin of the right internal thoracic artery (ITA) and a normal origin of the left ITA, both of which were demonstrated to be patent and did not follow a tortuous course. The CABG had involved revascularization of the left anterior descending artery (LAD) with the right ITA, and the obtuse marginal artery with the left ITA. The patient had an uneventful postoperative course and developed no respiratory symptoms.

We herein report the case of a 56-year-old man with idiopathic thrombocytopenic purpura who required an emergency aortic arch replacement. Intraoperatively, hemostasis was achieved using platelet transfusions. Postoperatively, the use of high-dose gamma-globulin therapy was able to maintain an adequate platelet count and good hemostasis.

Mitral valve replacement was performed through a right thoracotomy using femorofemoral bypass under profound systemic hypothermia in a 62-year-old man who had undergone coronary artery bypass grafting using both internal thoracic arteries. The right thoracotomy approach minimizes the risk of injury to the arterial grafts, and deep hypothermia obviates the need to interrupt the grafts to administer cardioplegia. This technique provides excellent exposure of the mitral valve while minimizing the operative risk.

The fecal bacterial flora was examined in multiple stool specimens from 14 subjects with gastrointestinal disorders before, during and after the oral administration of bifidobacterial preparation (BBG, viable B. breve and B. bifidum, 3 X 10(9) or 6 X 10(9) per day) for 2 or 3 weeks. Enumerations of fecal bacterial flora showed no conspicuous alterations in total anaerobic bacterial counts during the BBG therapy, however the total number of bifidobacteria in feces increased significantly, and of E. coli and other aerobacteria showed a tendency to decline. The administered B. breve and B. bifidum were recovered in the feces at a concentration of 10(8)/g and of 10(7) to 10(8)/g, respectively. Both species continued to be excreted over 2 weeks after completion of the medication in the feces at concentrations of 10(6) to 10(7)/g and of 10(5) to 10(6)/g respectively, and diminished rapidly in 5 patients and continued at essentially the same level as during the medication in 6 patients. During the treatment the pH, urease activity and ammonia content in feces became lowered and showed a rerise after therapy. Symptomatic discomforts including abdominal distension and pain, anorexia, edema and fever of undetermined origin were reduced during the therapy. Urinalysis, hematological examinations and blood biochemical tests including blood ammonia level, however revealed no significant change.

Objectives: Use of the free gastroepiploic artery graft for coronary revascularization has not been very popular because of its inclination toward vasospasm. We hypothesized that the cause of free gastroepiploic artery spasm was the graft damage caused by an interruption of venous drainage from the graft. To solve this problem, we developed a new method of free gastroepiploic artery grafting. Methods: From January 1997 to October 1999, 33 patients underwent coronary artery bypass grafting with the free gastroepiploic artery according to our new method. The gastroepiploic artery graft was harvested en bloc with its satellite veins. The gastroepiploic vein was anastomosed to the right atrial appendage for venous drainage simultaneously with the gastroepiploic artery being grafted in the aortocoronary position. Results: A total of 96 distal anastomoses were performed, including 33 free gastroepiploic artery grafts according to our method, 33 in situ left internal thoracic artery grafts, 26 saphenous vein grafts, and 4 radial artery grafts. Neither operative nor hospital death occurred. Early postoperative angiography revealed that all of the 33 free gastroepiploic artery grafts performed with our method were patent without spasm, and flow competition occurred only in 2 of those grafts. On late angiography, all 15 free gastroepiploic artery grafts were patent without spasm. Conclusions: The free gastroepiploic artery grafting with venous drainage technique we developed can prevent graft spasm, leading to improved patency rate. (J Thorac Cardiovasc Surg 2001;121:520-5)

A rare case of granular cell ameloblastoma in the anterior mandible of a 59-year-old man has been studied by light and electron microscopy. In some areas, the tumor was very similar to an oncocytoma (oxyphilic adenoma). Almost all tumor cells were full of eosinophilic granules, whereas in the common type of granular cell ameloblastoma, only the cells located in the central portion of the tumor are granular.

Oral tryptophan loading tests were performed on patients with cirrhosis of the liver before and after treatment with an oral antibiotic practically unabsorbed from the gastrointestinal tract. After antibiotic therapy, neuropsychiatric manifestations evoked by the oral administration of tryptophan were reduced in duration by about 50% and in severity as well despite a slightly enhanced elevation of serum total and free tryptophan levels, compared to pre-treatment loading tests. The urinary indican output also showed a significantly greater decrease in the post-treatment test (p less than 0.05) whereas no appreciable difference was observed in urinary 5-hydroxy-indoleacetic acid excretion between the pre- and post-treatment tests. The data suggest that neuropsychiatric manifestations seen following oral administration of tryptophan may be attributed to intestinal tryptophan metabolites rather than to this aromatic amino acid itself and/or its metabolites in the brain.