Dynamics of Oxidative Stress Evoked by Myocardial Ischemia Reperfusion After Off-Pump Coronary Artery Bypass Grafting Elucidated by Bilirubin Oxidation.

BACKGROUND: Revascularization therapy relieves myocardial ischemia, but can also result in ischemia-reperfusion injury caused by oxidative stress. However, the biokinetics of oxidative stress after myocardial ischemia-reperfusion are uncertain. This study aimed to evaluate the dynamics of oxidative stress after off-pump coronary artery bypass grafting (OPCAB) by measuring urinary biopyrrin levels. Biopyrrin is an oxidative metabolite of bilirubin thought to reflect oxidative stress, along with reactive nitrogen species (RNS).Methods and Results:The study included 18 patients who underwent OPCAB; patients were divided into effort angina pectoris (EAP; n=11) and unstable angina pectoris (UAP; n=7). Urinary biopyrrin and RNS levels were measured during the perioperative period (≤48 h after surgery). Biopyrrin levels transiently increased 4-12 h post-surgery (early phase), followed by a prolonged increase approximately 24-32 h post-surgery (late phase). The delayed increase in biopyrrin tended to be higher in patients with UAP, with a simultaneous increase in RNS. The patients in the UAP group had generally high pulmonary capillary wedge pressure (PCWP), although the cardiac index was within a normal range during the delay phase. CONCLUSIONS: The dynamics of biopyrrin levels revealed a biphasic pattern of oxidative stress after OPCAB. Delayed production of oxidative stress may be influenced by preoperative severity of myocardial ischemia and delayed RNS production.

Influence of vessel stenosis on indocyanine green fluorescence intensity assessed by near-infrared fluorescence angiography.

PURPOSE: Although useful for visualizing blood flow during revascularization surgery, the permeability of near-infrared fluorescence (NIR) angiography using indocyanine green (ICG) does not allow for vessel stenosis visualization. We hypothesized that changes in ICG fluorescence intensity reflect vessel stenosis, and evaluated the influence of stenosis on blood flow by ex vivo experimentation. METHODS: The vessel stenosis model comprised a silicon tube, a graft occluder, and artificial blood. During near-infrared angiography, the fluorescense intensity was calculated during pre- and post-stenosis of an artificial circuit, using a NIR angiography. We measured the maximum fluorescence intensity and the time to maximum fluorescence intensity. RESULTS: Severe stenosis (≥75%) attenuated the increase in ICG fluorescence intensity in the tube significantly, pre- and post-stenosis. The time to maximum fluorescence intensity did not differ between sites pre- and post-stenosis, irrespective of stenosis severity. CONCLUSION: Stenosis affected the ICG fluorescence intensity through the vessel. Thus, quantitative analysis using NIR angiography may detect severe vessel stenosis (≥75%), and the extinction curve of indocyanine fluorescence intensity may support the evaluation of blood flow. The absence of differences in the time to maximum fluorescence intensity for degrees of stenosis might suggest a limitation of previous conventional qualitative assessments.

Quantitative assessment technique of HyperEye medical system angiography for coronary artery bypass grafting.

PURPOSE: The HyperEye Medical System (HEMS) uses indocyanine green (ICG) to visualize blood vessels in coronary artery bypass grafting (CABG). We performed quantitative HEMS assessment to detect grafts at risk of occlusion. METHODS: We assessed the HEMS angiograms of 177 grafts from 69 patients who underwent CABG and compared the results with those of fluoroscopic coronary angiography, by measuring the increasing rate of ICG intensity, average acceleration value, and time to peak luminance intensity. RESULTS: Grafts in the patent and failed groups showed significant differences in their increasing rate of intensity and average acceleration value. The average accelerations value of ICG intensity of internal thoracic artery (ITA) and saphenous vein (SV) grafts were 112.3 and 144.9 intensity/s2 in the patent group, and 71.0 and 91.8 intensity/s2 in the failed group. The time to peak luminance intensity was 1.7 and 1.4 s in the patent group and 2.3 and 1.9 s in the failed group; these values were not significantly different. CONCLUSION: Significant reductions in the ICG intensity rate and average acceleration value can occur in failed grafts. Therefore, quantifiable changes in ICG intensity may help detect minute changes in blood flow.

[Ascending Aortic Thrombus Recognized by Acute Brachial Arterial Occlusion].

We report a case of ascending aortic thrombus with acute arterial occlusion of the brachial artery. A 49-year-old woman had sudden pain in her right arm due to acute occlusion of the right brachial artery. Contrast-enhanced computed tomography and echocardiography revealed a large mobile thrombus in the ascending aorta, which prompted surgical intervention. The thrombi were removed via aortotomy under circulatory arrest. Trans-esophageal echocardiography was useful for watching a potential detachment of the thrombus in the aorta during surgical manipulations or systemic perfusion. Despite no evidence of either inherited or acquired thrombotic predisposition, thrombosis in the right atrium and deep veins of the lower extremities was found postoperatively. Since antiplatelet and anticoagulant therapy was started, she has suffered from no thrombotic event.

Efficacy of intraoperative HyperEye Medical System angiography for coronary artery bypass grafting.

PURPOSE: When performing coronary artery bypass grafting, anastomotic insufficiency needs to be detected during surgery. We developed a novel indocyanine green angiography system, the HyperEye Medical System (HEMS), which enables color imaging of the bypass flow. This article described the accuracy of HEMS angiography for predicting graft patency. METHODS: A total of 144 grafts in 40 coronary artery bypass grafting patients were assessed by HEMS angiography, a transit time flowmeter (TTF) during surgery and fluoroscopic angiography 1 year after the operation. RESULTS: HEMS angiography showed normal flow in 133 grafts, but abnormal flow in 11. Fluoroscopic angiography showed that 130 of the 133 "normal" grafts were patent (negative predictive value: 97.7%) and that nine of the 11 "abnormal" grafts were occluded (positive predictive value: 81.8%). As a result, 134 grafts were assessed as normal and 10 as abnormal by TTF. Fluoroscopic angiography showed that 124 of these 134 grafts were patent (negative predictive value: 92.5%), whereas two of the 10 grafts were occluded (positive predictive value: 20.0%). For the 127 grafts with compatible results by the HEMS and TTF assessments, the positive and negative predictive values were 100 and 97.6%, respectively. CONCLUSION: HEMS angiography of a bypass graft may provide an accurate prediction of the graft patency after surgery.

[Operative Results of Total Arch Replacement with Arch First Technique using a Trifurcated Graft].

In aortic arch surgery, we reconstruct branches before opening the arch to avoid cerebral embolism of the debris derived from the aortic wall. We made a trifurcated graft for branch reconstruction using 10 mm and 8 mm polyester grafts. Cardiopulmonary bypass started under right axillary perfusion and venous drainage through the right atrium. While cooling, the left subclavian artery was clamped and anastomosed to the end of the trifurcated graft. Then the ascending aorta was cross-clamped and cardioplegic solution was infused. At 25 degrees centigrade of the tympanic temperature, the left carotid artery is clamped and anastomosed to the branch of the trifurcated graft with or without perfusion into the left carotid artery. Subsequently the brachiocephalic artery was reconstructed in the same manner. After antegrade cerebral perfusion was established through the trifurcated graft via right axillary perfusion, distal anastomosis of the aortic arch was done with the open distal technique. Graft-graft anastomosis was followed to reperfuse the lower half of the body. Finally proximal anastomosis was performed to complete total arch replacement. Forty-four patients underwent total arch replacement in this technique. In-hospital mortality was 4.5%. Cerebral infarction occurred in 4.5% of the patients probably due to embolization of the debris derived from the branches of the aortic arch.

Tamoxifen versus tamoxifen plus doxorubicin and cyclophosphamide as adjuvant therapy for node-positive postmenopausal breast cancer: results of a Japan Clinical Oncology Group Study (JCOG9401).

BACKGROUND: Cancer subtype has recently become an increasingly important consideration when deciding the treatment strategy for breast cancer. For the estrogen receptor positive (ER+) subtype, the efficacy of adjuvant endocrine therapy is definitive, but that of adjuvant chemotherapy is controversial. METHODS: In order to evaluate the effect of adding doxorubicin (A) and cyclophosphamide (C) to tamoxifen (TAM) (ACT) on the overall survival (OS) of node-positive postmenopausal breast cancer (PMBC) patients, we conducted a randomized trial. Eligibility criteria included pathologically node-positive (n = 1-9) PMBC, stage I-IIIA disease. Patients were randomized to receive either TAM (20 mg daily) for 2 years or A (40 mg/m(2)) and C (500 mg/m(2)) plus TAM (ACT) as adjuvant therapy following surgery. RESULTS: One hundred twenty-nine patients were recruited (TAM 64, ACT 65) between October 1994 and July 1999. The hazard ratios for OS and relapse-free survival (RFS) were 0.58 (95 % CI 0.24-1.39; log-rank p = 0.22) and 0.45 (95 %CI 0.24-0.86; log-rank p = 0.013), respectively, in favor of ACT. The 5-year OS and RFS were 76.9 % (ER+ 87.1 %, ER- 53.3 %) and 54.9 % (ER+ 59.3 %, ER- 42.9 %) for TAM and 85.0 % (ER+ 90.0 %, ER- 77.1 %) and 76.7 % (ER+ 76.9 %, ER- 76.0 %) for ACT. A higher proportion of the patients receiving ACT than those receiving TAM experienced grade 3 decreased white blood cell count and grade 2-3 nausea. CONCLUSION: The efficacy of adding AC to TAM was not high for ER+, node-positive PMBC. However, adjuvant ACT therapy was considered to be effective for ER-, node-positive PMBC.

Cardiac calcified amorphous tumor stuck in the aortic valve that mimicked a chameleon's tongue: report of a case.

A calcified amorphous tumor (CAT) is a rare intracardiac mass that carries a risk of embolism. We herein present the case of a club-shaped CAT that originated from the calcified mitral annulus. Echocardiography indicated a pendular motion of the mass and repeated entrapment by a stenotic aortic valve that was sustained for several beats, mimicking a chameleon's tongue. An emergency operation was performed because of the risk of embolism, as well as potential progression of cardiac failure due to worsening aortic valve stenosis. The histological findings were consistent with the diagnosis of a CAT. This report describes a case of an intracardiac tumor that showed unique motion like a chameleon's tongue.

[Pacemaker infection in a child; report of a case].

In the treatment for pacemaker infection, removal of infected devices and intensive antibiotics therapy are in principle and new devices should be implanted apart from the infected site. However, there are some problems in the case of children:it is not easy to remove infected devices because epicardial leads are often used for them. If endocardial leads are chosen as a new system, extension of the lead would be concerned with their growth. We report a pediatric case of infection of pacemaker using epicardial leads. It was difficult to cure infection by repeated local treatment leaving epicardial leads and antibiotics therapy was obliged to continue for 9 years to keep infection under control. After growing up, we implanted endocardial leads for her and removed infected devices to cure infection completely.

Intraoperative continuous hemodiafiltration with selective venous drainage of ischemic limbs.

We report two cases of acute limb ischemia with threatened myonephropathic metabolic syndrome (MNMS) in which continuous hemodiafiltration (CHDF) was started before revascularization with selective drainage from the clamped femoral vein of ischemic limb and return of processed blood into the contralateral femoral vein. It was aimed to optimise the removal of metabolites which were produced by myolysis following reperfusion as well as to minimize the deviation of metabolites into the systemic circulation. Both cases had uneventful postoperative course without MNMS and the limbs were salvaged.

Development of a new selective coronary perfusion cannula.

The two most common types of coronary perfusion cannulae currently being used are the "balloon type", with a balloon at the tip, and the "fenestrated type", which has holes along the side near the tip. However, on occasion an unusually high perfusion pressure or a considerable amount of leakage is encountered during infusion of the cardioplegic solution. We have examined the properties of a newly developed Kochi Medical School (KMS)-type cannula and compared these to the properties of the balloon-type and fenestrated-type cannulae in an ex vivo experimental model that contains ostia of 4, 3, or 2 mm in diameter. Ejected flow velocity, circuit pressure, and the amount of leakage were measured at an infusion rate of 100 and 200 mL/min, with the latter two parameters measured under the counterpressure of 0 and 50 cmH2O to examine the influence of coronary vascular resistance. Without counterpressure, the balloon type presented with the highest flow velocity (263 cm/s at 200 mL/min) and perfusion pressure (64 mmHg at 200 mL/min) but without leakage. The fenestrated type yielded a considerable amount of leakage (40 % at an ostium size of 2 mm). The KMS type showed a lower flow velocity and circuit pressure with less leakage. Under 50 cmH2O counterpressure, however, only the KMS-type cannula could inject the water to any ostium size at both flow rates. These results suggest that the concept of the KMS-type cannula may be advantageous to achieving a secure infusion to a diseased coronary ostium.

Impact of real-time virtual sonography, a coordinated sonography and MRI system that uses an image fusion technique, on the sonographic evaluation of MRI-detected lesions of the breast in second-look sonography.

The aim of this study was to verify the utility of second-look sonography using real-time virtual sonography (RVS)-a coordinated sonography with an MRI system that uses an image fusion technique with magnetic navigation-on the sonographic evaluation of MRI-detected lesions of the breast. Of the 196 consecutive patients who were examined with breast MRI in our hospital from 2006 to 2009, those patients who underwent second-look sonography to identify MRI-detected lesions were enrolled in this study. MRI was performed using a 1.5-T imager with the patient in a supine position. To assess the efficacy benefits of RVS, the correlations between lesion detection rates, MRI features, distribution, and histopathological classification on second-look sonography using conventional B-mode or RVS were analyzed. Of the 196 patients, 55 (28 %) demonstrated 67 lesions initially detected by MRI, followed by second-look sonography. Of the 67 MRI-detected lesions, 18 (30 %) were identified with second-look sonography using conventional B-mode alone, whereas 60 (90 %) lesions were detected with second-look sonography using RVS (p < 0.001). The detection rates of 16 focal lesions, 46 mass lesions, 16 lesions sized <5 mm, 45 lesions sized 5-10 mm, 26 lesions situated within the mammary gland, 41 lesions situated around mammary fascia, 24 malignant lesions, and 43 benign lesions were, respectively, 25, 26, 25, 24, 42, 17, 33, and 23 % by conventional B-mode, and were significantly higher, respectively, at 94, 89, 94, 89, 88, 90, 92, and 88 % by RVS. Of the seven lesions with no sonographic correlates, five could be biopsied by marking MRI information onto the body surface using RVS. Overall, 65 of 67 (97 %) MRI-detected lesions were confirmed by histopathological results. Our results suggest that the additional use of RVS on second-look sonography significantly increases the sonographic detection rate of MRI-detected lesions without operator dependence.

A case of estrogen receptor positive secretory carcinoma in a 9-Year-old girl with ETV6-NTRK3 fusion gene.

The patient was a 9-year-old premenarcheal pediatric female, whose chief complaint was a well-circumscribed palpable right breast mass without nipple discharge. Although the patient had noticed the lump 2 years prior to hospital admission, its size (1.5 × 1.3 cm) had been stable. There was no family history or previous history of malignancies. Physical examination showed a well-delimited, elastic-firm and movable tumor just beneath the nipple and areolar complex. Regional lymph nodes were not palpable. Ultrasonography and breast computed tomography revealed a subareolar oval-shaped tumor exhibiting homogeneous echogenicity with clear margins. Distant metastases could not be detected using whole-body computed tomographic scans. A fine-needle aspiration cytology specimen showed atypical cells with prominent nucleoli and abundant intracellular secretory material, suggesting the possibility of secretory carcinoma. Histopathological analysis of the core needle biopsy specimen revealed that the tumor was a secretory carcinoma. The patient underwent total mastectomy with sentinel lymph node biopsy. Metastases were not observed in the removed lymph nodes. Estrogen receptor was weakly positive and progesterone receptor was negative. Human epidermal growth factor receptor 2 expression was also negative. In addition, the ETV6 (exon 5) and NTRK3 (exon 13) fusion gene was detected using the reverse transcription-polymerase chain reaction method. This gene is considered specific for secretory carcinoma. Immunohistochemistry revealed weak basal differentiation [cytokeratin 5/6(CK5/6)(+), vimentin(+) and epidermal growth factor receptor(+)]. The patient has received no adjuvant therapy and is currently disease free at 12 months after surgery.

Prognostic factors in young Japanese women with breast cancer: prognostic value of age at diagnosis.

OBJECTIVE: The primary objective of this study was to verify whether breast cancer patients aged <35 at diagnosis have poorer prognoses than those aged 35-39, in other words, to identify the prognostic value of age in younger premenopausal patients under 40 years old. The secondary objective was to assess prognostic factors specific for younger premenopausal patients. METHODS: We identified 242 consecutive patients who were diagnosed with stage I-III breast cancer before the age of 40 and underwent surgery between 1990 and 2004. We compared disease-free survival and overall survival in patients aged <35 years and those aged 35-39 years, and evaluated clinicopathological factors associated with disease-free survival or overall survival in each age group and in all patients under the age of 40. RESULTS: Ninety-nine (41%) patients were younger than 35 years and 143 (59%) were between 35 and 39 years. No significant difference in disease-free survival or overall survival was found between the two groups. In our cohort of patients under the age of 40, the independent factors associated with poor disease-free survival and overall survival included positive axillary lymph nodes and triple-negative status, but not age at diagnosis. Adverse prognostic factors also did not differ considerably between the two age groups. CONCLUSIONS: Age at diagnosis was not an independent prognostic factor in our study. Our findings suggest that other clinicopathological features rather than age should be used to determine individualized treatment courses for breast cancer patients younger than 40 years.

[Introduction, designs and assessment of a suture set for standard cardiovascular surgery].

A packing system for threads and needles has been introduced with the aim of efficient operations in the field of cardiovascular surgery. To provide competent and safe surgery to patients, a suture set was developed according to the standard cardiovascular surgery procedure with cooperation between doctors and nurses at Kochi University Hospital. This suture set was introduced to all surgeries for adults conducted under cardiopulmonary bypass. Herein, we describe problems before the introduction, the process of the introduction, and designs of the suture set. In addition, we assessed the present condition since the introduction of this suture set. Many positive opinions were obtained from both doctors and nurses, and the suture set thus yielded a satisfactory assessment. Psychological stability and safety provided by the suture set may lead not only to cost reduction but also to an increased level of surgery as a whole. In addition, it may now be possible to provide simpler and more efficient cardiovascular surgery with this set. This suture set will serve as a useful model for thread and needle packing systems to be developed at various facilities in the future.

[Chemotherapy of a 2-week S-1 administration followed by 1-week rest for advanced and metastatic breast cancer].

When treating advanced and metastatic breast cancer patients with chemotherapy, it is mandatory to maintain the patients quality of life while keeping an acceptable level of antitumor activity. For these purposes, oral administration of S-1, fluorinated pyrimidine, is a good choice of treatment. Conventionally, a 4-week administration followed by a 2-week rest has been the treatment of choice with S-1. However, we applied a new regimen for 16 patients with advanced and metastatic breast cancer, in which one course consisted of a 2 week-administration followed by a week of rest, repeated twice. The median age of the patients who received this treatment was 59 years old(range 46. 8-80. 6). The response rate was 31. 2%, and the median values of time to progression and overall survival were 5. 1 and 17. 9 months, respectively. One case of thrombocytopenia as an adverse event was recognized. Our new S-1 regimen is likely to show an acceptable anti-tumor effect with minimal adverse events. The fidings suggest that this new regimen is clinically applicable for advanced and metastatic breast cancer patients.

Fusion of MRI and sonography image for breast cancer evaluation using real-time virtual sonography with magnetic navigation: first experience.

OBJECTIVE: We recently developed a real-time virtual sonography (RVS) system that enables simultaneous display of both sonography and magnetic resonance imaging (MRI) cutaway images of the same site in real time. The aim of this study was to evaluate the role of RVS in the management of enhancing lesions visualized with MRI. METHODS: Between June 2006 and April 2007, 65 patients underwent MRI for staging of known breast cancer at our hospital. All patients were examined using mammography, sonography, MRI and RVS before surgical resection. Results were correlated with histopathologic findings. MRI was obtained on a 1.5 T imager, with the patient in the supine position using a flexible body surface coil. Detection rate was determined for index tumors and incidental enhancing lesions (IELs), with or without RVS. RESULTS: Overall sensitivity for detecting index tumors was 85% (55/65) for mammography, 91% (59/65) for sonography, 97% (63/65) for MRI and 98% (64/65) for RVS. Notably, in one instance in which the cancer was not seen on MRI, RVS detected it with the supplementation of sonography. IELs were found in 26% (17/65) of the patients. Of 23 IELs that were detected by MRI, 30% (7/23) of IELs could be identified on repeated sonography alone, but 83% (19/23) of them were identified using the RVS system (P = 0.001). The RVS system was able to correctly project enhanced MRI information onto a body surface, as we checked sonography form images. CONCLUSIONS: Our results suggest that the RVS system can identify enhancing breast lesions with excellent accuracy.

[Importance of the primary physician for pain management in patients with recurrent advanced cancer--a questionnaire survey].

With the objective of clarifying points that needed improvement to provide earlier and better treatment of pain by assessing the current state of cancer pain management in Japan, we conducted a questionnaire survey about pain management in patients with advanced/recurrent cancer who were suffering from pain. The results of the survey revealed that it is important for primary physician to place greater emphasis on pain management when treating cancer patients, to inform patients that the doctor should always be told if the patient has pain, and provide appropriate information about medical narcotics to their patients. The team approach to management of cancer has been increasing in importance recently. This survey suggested it is important for primary physicians, who play a central role in such teams, to listen to their patients' complaints about symptoms including pain. Furthermore, it should be remembered that patients are eager to establish a good, trusting relationship with their primary physician.

Phase III study to evaluate the use of high-dose chemotherapy as consolidation of treatment for high-risk postoperative breast cancer: Japan Clinical Oncology Group study, JCOG 9208.

A randomized controlled trial was conducted to evaluate the efficacy of high-dose chemotherapy (HDC) as consolidation of the treatment of high-risk postoperative breast cancer. Patients under 56 years of age with stage I to IIIB breast cancer involving 10 or more axillary lymph nodes were eligible. The primary endpoint was relapse-free survival (RFS). Between May 1993 and March 1999, 97 patients were enrolled, and two patients became ineligible. The median age of the 97 patients was 46 years (range 27-55 years), and 72 (74%) were premenopausal. The median number of involved axillary nodes was 16 (range 10-49). All patients had undergone a radical mastectomy. Major characteristics were well balanced between the treatment arms. Forty-eight patients in the standard-dose (STD) arm received six courses of cyclophosphamide, doxorubicin, and 5-fluorouracil followed by tamoxifen. Forty-nine patients were assigned to undergo HDC with cyclophosphamide and thiotepa after six courses of cyclophosphamide, doxorubicin, and 5-fluorouracil followed by tamoxifen; however, 15 of these patients (31%) did not undergo HDC. HDC was well tolerated without any treatment-related mortality. At a median follow-up of 63 months, the 5-year RFS of 47 eligible patients in the STD arm and 48 eligible patients in the HDC arm was 37% and 52% on an intent-to-treat basis, respectively (P = 0.17). Five-year overall survival of all randomized patients was 62% for the STD arm and 63% for the HDC arm (P = 0.78). Although the prespecified values of the two arms were not so accurate as to allow detection of the observed difference, no advantage of HDC was observed in terms of RFS or overall survival.