Effect of hepatic arterial infusion chemotherapy of 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma in the Nationwide Survey of Primary Liver Cancer in Japan.

BACKGROUND: The efficacy of hepatic arterial infusion chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC) remains unclear. METHODS: The outcome of 476 patients with HCC who underwent hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin (HAIC) were compared with 1466 patients who did not receive active therapy. RESULTS: A survival benefit of the therapy after adjusting for known risk factors was observed (hazard ratio, 0.48; 95% CI, 0.41-0.56; P<0.0001). In propensity score-matched analysis (n=682), median survival time was longer for patients who underwent chemotherapy (14.0 months) than for patients who did not receive active treatment (5.2 months, P<0.0001). CONCLUSION: For advanced HCC, HAIC is considered to be an effective treatment.

Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma.

BACKGROUND: We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort. METHODS: In the current retrospective cohort study, we measured serum levels of the eight cytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS). RESULTS: Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95% CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30-3.06) and OS (HR, 1.94; 95% CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis. CONCLUSION: High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.

Isolation and characterization of a novel short peptide associated with Crohn's disease.

Phage display technology has been utilized to select target molecules against circulating antibodies. The aims of this study were to isolate a peptide that binds with serum from Crohn's disease (CD) patients and to examine its diagnostic and pathogenic significance. A phage display library was constructed using cDNA from Caco-2 cells. Affinity selection using this cDNA library and serum samples from patients with CD was then performed. Phage clones that specifically reacted with the CD sera were then selected using a phage enzyme-linked immunosorbent assay (ELISA). After the DNA sequences of the selected phages were determined and converted to amino acid sequences, the synthesized peptides were examined using an ELISA. The effect of the synthesized peptides on cytokine release from cultured blood mononuclear cells was investigated. An ELISA analysis for TCP-353 demonstrated that while 61·7% of the samples from CD patients were seroreactive, seroreactivity was less common among patients with ulcerative colitis (7·3%), acute colitis (0%) or colon cancer (11·4%) and among normal subjects (2·8%). The induction of interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α release, but not IL-10 release, in response to TCP-353 peptide was enhanced in CD mononuclear cells only. We isolated a novel peptide that specifically binds to CD sera and stimulates the proinflammatory responses of CD mononuclear cells. TCP-353 may have diagnostic, pathogenic and therapeutic significance with regard to the treatment of CD.

[Infective endocarditis with acute embolism to the lower extremity artery caused by a vegetation: report of a case].

Successful surgical treatment of a case of infective endocarditis with embolism to a lower extremity artery is reported. A 71-year-old man was referred to our hospital for the treatment of infective endocarditis. Echocardiography showed a vegetation on the non-coronary cusp of the aortic valve measuring 19 mm in diameter. We planned surgical treatment, including aortic valve replacement, however, embolism of a lower extremity artery by the vegetation occurred during the waiting period for the operation. We removed the offending vegetation from the popliteal artery and replaced the peccant aortic valve with a prosthetic valve in separate operations. The postoperative course was uneventful and the patient was transferred to another hospital on the 33rd day after the valve replacement surgery.

Rejection of cardiac xenografts transplanted from alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs to baboons.

The use of alpha1,3-galactosyltransferase gene-knockout (GalT-KO) swine donors in discordant xenotransplantation has extended the survival of cardiac xenografts in baboons following transplantation. Eight baboons received heterotopic cardiac xenografts from GalT-KO swine and were treated with a chronic immunosuppressive regimen. The pathologic features of acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR) and chronic rejection were assessed in the grafts. No hyperacute rejection developed and one graft survived up to 6 months after transplantation. However, all GalT-KO heart grafts underwent graft failure with AHXR, ACXR and/or chronic rejection. AHXR was characterized by interstitial hemorrhage and multiple thrombi in vessels of various sizes. ACXR was characterized by TUNEL(+) graft cell injury with the infiltration of T cells (including CD3 and TIA-1(+) cytotoxic T cells), CD4(+) cells, CD8(+) cells, macrophages and a small number of B and NK cells. Chronic xenograft vasculopathy, a manifestation of chronic rejection, was characterized by arterial intimal thickening with TUNEL(+) dead cells, antibody and complement deposition, and/or cytotoxic T-cell infiltration. In conclusion, despite the absence of the Gal epitope, acute and chronic antibody and cell-mediated rejection developed in grafts, maintained by chronic immunosupression, presumably due to de novo responses to non-Gal antigens.

Development of granulocyte and monocyte adsorptive apheresis in the rat dextran sodium sulfate-induced colitis model.

Granulocytapheresis (GCAP) selectively removes large numbers of granulocytes and monocytes from peripheral blood by adsorptive apheresis, and in patients with ulcerative colitis GCAP has been associated with significant efficacy. However, the mechanism(s) of efficacy of this strategy is poorly understood. This rat model of dextran sodium sulfate (DSS)-induced colitis was to investigate the effect of GCAP on tumor necrosis factor (TNF)-alpha release by peripheral leukocytes. By using mini columns, an experimental GCAP setting was developed and applied to the DSS-induced colitis model. The production of TNF-alpha by lipopolysaccharide-activated leukocytes in whole blood was measured by enzyme-linked immunosorbent assay. In rats that received GCAP with columns containing leukocytapheresis carriers, TNF-alpha release by leukocytes was significantly (p < 0.05) suppressed, while no change in TNF-alpha production was seen in rats that received GCAP with sham columns. This first experimental setting in the rat colitis model suggests that GCAP is feasible in animals and should shed light on the mechanism(s) of GCAP in clinical settings. Given that TNF-alpha is a major inflammatory cytokine, down-modulation of TNF-alpha might represent one mechanism of antiinflammatory effects of GCAP.

Troponin T levels in baboons with pig heterotopic heart transplants.

Troponin T levels have been monitored in baboons (n = 8) undergoing pig heterotopic heart transplantation, and correlated with a decrease in graft contractions and graft survival. Pig heart graft survival was from 12 to 139 days (mean 45, median 33), and graft failure was associated with predominant thrombotic microangiopathy and ischemia, with focal hemorrhage, and edema. An increase in troponin T levels 5 to 6 days before graft failure correlated closely with diminished graft contractions. An increase in troponin T was a reliable indicator that graft dysfunction was occurring.

Potential of aspirin to inhibit thrombotic microangiopathy in alpha1,3-galactosyltransferase gene-knockout pig hearts after transplantation in baboons.

Hearts from alpha1,3-Galactosyltransferase gene-knockout (GaIT-KO) pigs were transplanted heterotopically into 8 baboons that received an anti-CD154 monoclonal antibody (mAb)-based immunosuppressive regimen and heparin. Three baboons died or were euthanized with beating grafts on 16, 23, and 56 days, respectively, and the remaining 5 grafts functioned for 59-179 days. Hyperacute rejection did not occur, and classical features of acute humoral xenograft or acute cellular rejection were rare. However, thrombotic microangiopathy (TM) developed in all cases; its onset was delayed in 2 baboons that received aspirin. Function of a pig organ in a baboon for a period approaching 6 months has not been reported previously and lends encouragement that the barriers to xenotransplantation will be overcome, but TM requires investigation.

Performance of the EuroSCORE II and the Society of Thoracic Surgeons Score in patients undergoing aortic valve replacement for aortic stenosis.

Aim. The aim of this study was to evaluate the performance of the new European System for Cardiac Operative Risk Evaluation (EuroSCORE) II and the Society of Thoracic Surgeons (STS) score in patients undergoing aortic valve replacement (AVR) for aortic stenosis (AS). This study also evaluated the performance of the EuroSCORE II in high-risk patients. Methods. Three hundred and six consecutive adult patients underwent AVR with or without coronary artery bypass grafting at our institution from August 2002 to June 2012. The cut-off value of 6% for the EuroSCORE II and 10% for the STS score was used to identify high-risk in this study. Results. Operative mortality was 3.5% (N.=11). The mean expected mortality for all patients was 3.1% (O/E ratio=1.12) for the EuroSCORE II and 5.1% (O/E ratio=0.68) for the STS score. Observed versus expected mortality for the high-risk patients was 17.2% versus 11.9% (O/E ratio=1.44) for the EuroSCORE II (N.=29) and 19.3% versus 18.5% (O/E ratio=1.04) for the STS score (N.=31), and that for the low-risk was 2.1% versus 2.2% (O/E ratio=0.95) for the EuroSCORE II and 1.8% versus 3.5% (O/E ratio=0.51) for the STS score. Discrimination power of the STS score was good (area under the receiver operating characteristics curve [AUC] 0.74), but that of the EuroSCORE II was suboptimal (AUC 0.66). Conclusion. Good calibration ability of the EuroSCORE II for low-risk patients and that of the STS score for high-risk are observed. However, the EuroSCORE II underestimates the operative mortality in high-risk patients and the STS score overestimates the risk in low-risk patients.

Graft replacement for huge aneurysm of the main pulmonary artery.

We present 2 cases of huge aneurysm of the main pulmonary artery without significant pulmonary artery hypertension or intracardiac shunt. Both patients underwent surgery where resection of the aneurysm and graft replacement, using Hemashield prosthesis (Meadox Medicals, Oakland, NJ), was performed. They are now leading normal lives without any symptoms.

Ten years' experience of aortic valve replacement with the Omnicarbon valve prosthesis.

BACKGROUND: There are few clinical studies on late follow-up of the Omnicarbon monoleaflet valve. We report our 10-year experience with this valve in the aortic position and also compare late hemodynamic performance of this valve with that of the CarboMedics valve in the aortic position. METHODS: From January 1985 to June 1995, 117 consecutive patients underwent aortic valve replacement (AVR) with the Omnicarbon valve. There were 66 men and 51 women aged 13 to 69 years (mean age, 50 +/- 12 years). They were divided into three groups: group 1 (43 patients) had isolated AVR, group 2 (36) had AVR and concomitant operations, and group 3 (38) had combined AVR and mitral valve replacement. Follow-up was 96.6% complete and consisted of 882.7 patient-years (range, 2.5 to 10.6 years; mean follow-up, 7.5 +/- 2.7 years). RESULTS: There were three early deaths (2.6%) and 18 late deaths (2.0%/patient-year) ten of which were due to valve-related causes and eight, non-valve-related causes. Survival rates at 10 years in groups 1, 2, and 3 were 77.6%, 82.4%, and 78.6%, respectively. The overall rates of freedom from valve-related complications in groups 1, 2, and 3 at 10 years were 77.4%, 100%, and 80.9%, respectively. The rates of freedom from the following complications in groups 1, 2, and 3 at 10 years were as follows: thromboembolism--94.8%, 100%, and 89.4%, respectively; valvar thrombosis--95.0%, 100%, and 100%; anticoagulant-related hemorrhage--93.6%, 100%, and 93.4%; prosthetic valve endocarditis--93.0%, 100%, and 97.2%; and reoperation--90.6%, 100%, and 97.2%. There were no significant differences between groups. All survivors showed marked improvement in New York Heart Association functional class, from 86% in classes III and IV preoperatively to 96% in classes I and II postoperatively. The Omnicarbon valve exhibited no significant difference in hemodynamic performance after isolated AVR compared with the CarboMedics bileaflet valve at the same follow-up periods. CONCLUSIONS: This 10-year study confirms that the Omnicarbon valve is a durable prosthesis and provides excellent functional improvement with low rates of thromboembolism and valvar thrombosis in the aortic position.

Tricuspid valve surgery for functional tricuspid valve regurgitation associated with left-sided valvular disease.

OBJECTIVES: We have reviewed 260 patients who underwent initial tricuspid valve surgery for functional tricuspid valve regurgitation (TR) and analyzed independent predictors for early and late unfavorable results. MATERIALS AND METHODS: Between 1981 and 1998, 260 tricuspid valve operations were performed for functional TR. There were 94 males and 166 females with a mean age of 55 years. The tricuspid valve surgery procedures consisted of De Vega tricuspid annuloplasty in 240 patients, ring annuloplasty in four patients, and tricuspid valve replacement in 16 patients. The mean duration of follow-up was 7.8 years. RESULTS: Hospital mortality was 8.9% (23 patients). Late deaths occurred in 34 patients including cardiac-related late deaths in 26 patients. The survival rates were 83+/-2% at 5 years and 78+/-3% at 10 years. Late tricuspid valve reoperation was performed on 13 patients due to residual or recurrent TR in 12 patients and thrombosed tricuspid bileaflet mechanical valve in one patient. The tricuspid valve reoperation-free survival rate was 90+/-2% at 5 years and 84+/-3% at 10 years. The only predictor of hospital mortality was preoperative highly elevated right atrial pressure (P=0.01). Variables predictive of cardiac-related late death were preoperative New York Heart Association (NYHA) class IV (P=0.01) and poor left ventricular ejection fraction (LVEF) (P=0.02). Residual TR of more than grade 2+ early after tricuspid annuloplasty was a significant risk factor for late tricuspid valve reoperation (P=0.01). Preoperative TR of grade 4+ was predictive of early residual TR (P=0.04). CONCLUSIONS: Tricuspid valve surgery for functional TR can be performed with acceptable levels of early mortality. Cardiac-related late mortality after tricuspid surgery may be improved by earlier surgical treatment before NYHA class IV or deterioration of LVEF occurs. To prevent late tricuspid reoperation, it is important not to leave residual TR of grade 2+ or more after tricuspid annuloplasty.

Endoventricular circular patch plasty for end-stage valvular cardiomyopathy.

We present here a case of end-stage non-ischemic valvular dilated cardiomyopathy (DCM) associated with mitral regurgitation (MR). The patient underwent surgery where left ventricular volume reduction using endoventricular circular patch plasty (EVCPP) and mitral valve replacement (MVR) were performed. He has improved much after the operation and is now in New York Heart Association (NYHA) functional class II.

Surgical repair of the pulmonary trunk aneurysm.

OBJECTIVE: Aneurysm formation of the pulmonary trunk is rare and there is controversy about optimal treatment for this disease. The aim of this article is to report four patients with pulmonary trunk aneurysm which were managed by surgical repair. MATERIALS AND METHODS: From 1986 to 1997, we performed surgical repair for pulmonary trunk aneurysm in four patients. There was one male and three female patients with a mean age of 63.3 years (range: 54-78 years). Concomitant diseases were cardiac valvular disease in four patients, thoracic aortic dissection in two, atherosclerotic abdominal aortic aneurysm in two, and coronary artery disease in one. All patients were in New York Heart Association functional class III preoperatively. Surgical procedures for the pulmonary trunk aneurysm included Dacron graft replacement in two patients and aneurysmorrhaphy in two. Associated procedures were cardiac valvular operation in three patients with four lesions and right ventricular outflow tract reconstruction (RVOTR) in one. RESULTS: There were no operative mortalities and no late deaths with a mean follow-up period of 6.6 years (range: 2.4-10.0 years). One female patient developed recurrent pulmonary trunk aneurysm 9.5 years after aneurysmorrhaphy, and underwent a second operation where Dacron graft replacement of the aneurysm including pulmonary valve replacement was performed successfully. All patients are now leading normal lives. CONCLUSIONS: Surgical management should be considered for large aneurysm of the pulmonary trunk regardless of its etiology and underlying disease to prevent possible rupture with fatal result if the patient has an acceptably low operative risk.

Early and late results of mitral valve repair for mitral valve regurgitation. Significant risk factors of reoperation.

BACKGROUND: Mitral valve repair for mitral valve regurgitation has many advantages over mitral valve replacement. However, durability and reoperation after mitral valve repair still remain major problems. We examined the outcome of mitral valve repair for mitral valve regurgitation and analyzed several pre- and intraoperative potential risk factors to determine the significant risk factors of reoperation. METHODS: From February 1981 to November 1996, 86 patients underwent mitral valve repair for mitral regurgitation or combined mitral regurgitation and stenosis. The mean age was 53 years, and 88.4% were New York Heart Association class III or IV. The causes of mitral valve disease were degenerative disease in 53 patients, rheumatic disease in 15, infective endocarditis in 11, and ischemic disease in 7. There were 2 early and 8 late deaths. RESULTS: Actuarial overall survival including early death at 10 years was 83.2+/-6.1%, freedom from reoperation was 86.8+/-5.3%, freedom from thromboembolism was 90.9+/-6.2%, and freedom from infective endocarditis was 98.5+/-1.5%. There was no bleeding event. At the last follow-up, most patients were in New York Heart Association class I or II. Prolapse of anterior leaflet and rheumatic mitral regurgitation were identified as independent predictors for reoperation. CONCLUSIONS: The repair techniques for anterior leaflet prolapse and patient selection in rheumatic mitral disease are important for improving long-term results of mitral valve repair for mitral regurgitation.

Lazaroid U74389G ameliorates ischemia-reperfusion injury in the rat lung transplant model.

We investigated the effect of Lazaroid U74389G on ischemia-reperfusion injury in the rat orthotopic left lung transplantation model. Five groups of reperfused lungs were studied. In group I, donor lungs were transplanted after 12 hours of preservation in University of Wisconsin (UW) solution at 4C. In groups II, III, and IV, Lazaroid was intravenously administrated at a dose of 1 mg/kg, 8 mg/kg, and 15 mg/kg, respectively, to the donors 30 minutes before preservation and also to the recipients 30 minutes before reperfusion after 12 hours of storage in UW solution at 4C. In group V, Lazaroid was added to the UW solution (80 micromol/l), and also was administered intravenously (6 mg/kg) 30 minutes before reperfusion. After 1 hour of reperfusion, gas exchange function and tissue lipid peroxide levels were significantly improved in Lazaroid-treated groups III, and V compared with no treatment group I. Histologic damage was less severe in groups III, IV, and V than in group I. These findings suggest that Lazaroid U74389G ameliorates ischemia-reperfusion injury in the rat lung transplants by inhibiting lipid peroxidation, regardless of whether it is administrated intravenously or given as an additive to the preservation solution.

[A novel instrument for off-pump coronary artery bypass grafting: traction-type coronary artery stabilizer].

A new instrument for heart stabilization during beating coronary bypass grafting without cardiopulmonary bypass and a clinical experience of off-pump LITA-to-LAD bypass using this mechanical stabilizer are described. This device provide optimal motionless field by traction mechanism in which traction sutures placed proximal and distal to the target coronary artery are tied to the U-shaped foot plate with multiple small holes. The advantages of this stabilizer are as follows; no need of heart compression, ability to displace the target lesion to facilitate anastomosis, reusable, compact size and easy handling. We believe this novel instrument will improve the anastomosis quality in patient undergoing coronary artery bypass without cardiopulmonary bypass.

[Early and late results of surgical intervention for 32 active infective endocarditis patients in last 10 years].

Thirty-two active infectious endocarditis patients who underwent 36 surgical procedures (23 NVEs, 13 PVEs) in last 10 years were reviewed. Seven patients (19.4%) died early postoperatively, 3/23 (13%) in NVEs and 4/13 (31%) in PVEs, and the causes of death were LOS in 5, MOF in one and cerebral bleeding in one. NVE patients of double valve deterioration who developed cardiogenic shock had poor operative results, 3 death in 4 (75%) despite of circulatory assist. Aortic PVEs who underwent Danielson's translocation technique also showed 3 death in 4 (75%). Five in 25 survivors (20%) developed late death and 3 of them were related with reinfection of prosthetic valve. We concluded that surgical treatment for active IE provides reasonable results, although they are still challenging for double valve NVEs and aortic PVEs, for which aortic root replacement using homograft would be the procedure of choice.

[Redo operation for recurrent pulmonary artery aneurysm associated with pulmonary stenosis and regurgitation].

A 63-year-old woman who underwent surgical correction of a recurrent pulmonary artery aneurysm associated with pulmonary stenosis and regurgitation is reported. On April 1986, she underwent commissurotomy of pulmonary valve, reconstruction of right ventricle out flow tract using a Polystan monocusp patch and pulmonary aneurysmorrhaphy for pulmonary artery aneurysm. Pathological examination of the resected pulmonary arterial wall revealed mucoid degeneration of media and fragmentation of elastic fiber. Nine years after the operation, recurrence of pulmonary artery aneurysm, pulmonary stenosis and regurgitation were recognized. On September 1995, she underwent redo operation with graft replacement of pulmonary artery and pulmonary valve replacement using woven Dacron prosthesis containing a Carpentier-Edwards bioprosthetic valve. We should choose as an initial procedure with graft replacement for pulmonary artery aneurysm with fragility of the pulmonary arterial wall. She is now doing very well at one year and 5 months after the redo operation.

[Clinical experience in 3 cases, 5 events of thrombosed Björk-Shiley mitral prostheses].

We have successfully treated 3 cases, 5 events of thrombosed Björk-Shiley mitral prostheses. Case 1: Treatment with urokinase thrombolytic therapy failed to improve the valve opening, and then submergent surgical thrombectomy was performed successfully. Case 2: This case was recurrent thrombosed valve. First time thrombosis was successfully managed by urokinase thrombolytic therapy. Second time thrombosis was treated with emergent surgical thrombectomy. Third time thrombosis was treated with urokinase thrombolysis and elective replacement of the Björk-Shiley valve with a 25 mm SJM valve. Case 3: Urokinase thrombolytic therapy failed to improve the valve function, and then emergent replacement of the Björk-Shiley valve with a 25 mm SJM valve was performed successfully. These cases suggested that the surgical treatment for the thrombosed Björk-Shiley mitral valve should be performed without delay in the patient whose condition is rapidly deteriorating.