Factors related to postoperative delirium in patients with lower limb ischaemia: a prospective cohort study.

OBJECTIVES: To preoperatively determine candidates at definitive risk of postoperative delirium (POD), we identified relevant factors in patients with arteriosclerosis obliterans who underwent bypass surgery. DESIGN: A prospective cohort study. PATIENTS AND METHODS: 299 patients (age ≥ 60 years) who underwent bypasses in 1995-2006 were enrolled. Cognitive impairment was assessed by the Revised Hasegawa Dementia Scale, the Confusion Assessment Method was also used, and severity was graded as Grade I-III (mild to severe) based on the Delirium Rating Scale. All patients were followed for 3 years. RESULTS: POD occurred in 88 patients (29%), with a median age of 75 (10) years (IQR). Onset was 2 (1) days postoperatively, and a duration of 2 (2) days was observed. POD was hyperactive in 89% and was Grade I, II, and III in 11%, 68%, and 21% respectively. Multiple logistic regression analysis identified the following risk factors for POD: age ≥ 72 years (<0.0001), end-stage renal failure (0.001), multiple occlusive lesions (<0.0001), cognitive impairment (0.003), and critical limb ischaemia (0.034). The 3-year survival rate was similar when comparing POD and non-POD patients (84% vs. 88%, NS). CONCLUSIONS: This study identified 5 risk factors for POD in patients undergoing bypasses for limb ischaemia. Long-term outcomes were similar when comparing the patients who experienced POD with those who did not.

Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?

OBJECTIVES: The aim of the study is to determine factors affecting ischaemic wound healing and role of the angiosome concept in bypass surgery. DESIGN: Single-centre, retrospective clinical study. MATERIALS AND METHODS: A total of 249 consecutive critical ischaemic limbs with tissue loss in 228 patients who underwent distal bypasses from 2003 to 2009 were reviewed. A total of 81% of patients were diabetic, and 49% of patients had dialysis-dependent renal disease (end-stage renal disease, ESRD). Distal targets of bypasses were the crural artery (57%) and the pedal artery (43%). RESULTS: The complete healing of ischaemic wounds was achieved in 211 limbs (84.7%). ESRD (odds ratio (OR) 0.127, p < 0.001), diabetes (OR 0.216, p = 0.030), Rutherford category 6 (R6) with heel ulcer/gangrene (OR 0.134, p < 0.001), R6 except heel (OR 0.336, p = 0.025) and low albuminaemia (OR 0.387, p = 0.049) were negative predictors of wound healing. Regarding the angiosome, the healing rate in the indirect revascularisation (IR) group was slower than in the direct revascularisation (DR) group, especially in patients with ESRD (p < 0.001). However, the healing rates of the DR and IR groups were similar after minimising background differences with propensity score methods (p = 0.185). CONCLUSIONS: In the field of bypass surgery, the angiosome concept seems unimportant, at least in non-ESRD cases. The location and extent of ischaemic wounds as well as co-morbidities may be more relevant than the angiosome in terms of wound healing.

Blood cardioplegia serves as a bicarbonate donor to the myocardium during ischemia: effects of anoxia and hypercapnia on acid-base characteristics of blood cardioplegic solution.

OBJECTIVES: We investigated the alterations of acid-base characteristics of the blood cardioplegia (BCP) solution during aortic cross-clamping in hearts arrested with BCP and during in vitro-simulated ischemia. METHODS: Following aortic cross-clamping, the hearts of 40 patients undergoing cardiac surgery were intermittently infused with an 18°C BCP solution and finally with a 34°C BCP solution prior to aortic cross-clamp release. We measured the pH, partial CO(2) pressure (pCO(2)), [HCO(3)(-)], and [Cl(-)] of the coronary sinus effluent in the final BCP solution. The BCP solution was assessed under in vitro gassing at 34°C with 95% N(2) + 5% CO(2) (n = 6), 50% N(2) + 50% CO(2) (n = 3), or 100% CO(2) (n = 6). RESULTS: The coronary sinus effluent, compared with the preinfusion BCP solution, exhibited a significantly lower pH and a greater pCO(2) with no change in the [HCO(3)(-)] level. In vitro, the 95% N(2) + 5% CO(2) gassing (simulated hypoxia) group exhibited a slight increase in [HCO(3)(-)] with no change in pCO(2) or pH whereas the 50% N(2) + 50% CO(2) gassing and the 100% CO(2) gassing (simulated hypoxia and hypercapnia) groups exhibited a significant increase in [HCO(3)(-)] under high pCO(2)-induced acidification. CONCLUSIONS: Under anoxia and CO(2) retention during aortic cross-clamping, the BCP solution can be a bicarbonate donor to the myocardium.

Randomized, double-blind, placebo-controlled clinical trial of hepatocyte growth factor plasmid for critical limb ischemia.

Hepatocyte growth factor (HGF) is a potent angiogenic factor. The efficacy and safety of intramuscular injection of a naked plasmid encoding human HGF gene (beperminogene perplasmid, Collategene) was investigated in patients with critical limb ischemia (CLI) in a multicenter, randomized, double-blind, placebo-controlled trial. The randomization ratio for plasmid to placebo was 2:1. Injection sites were selected in each patient limb based on angiographic findings. Placebo or plasmid was injected on days 0 and 28. Evaluation of efficacy was carried out after 12 weeks. The primary end point was the improvement of rest pain in patients without ulcers (Rutherford 4) or the reduction of ulcer size in patients with ulcer(s) (Rutherford 5). Secondary end points were ankle-brachial pressure index, amputation, and quality of life (QOL). Forty-four patients were treated, and we performed interim analysis of efficacy in 40 patients. The overall improvement rate of the primary end point was 70.4% (19/27) in HGF group and 30.8% (4/13) in placebo group, showing a significant difference (P=0.014). In Rutherford 5 patients, HGF achieved a significantly higher improvement rate (100% [11/11]) than placebo (40% [2/5]; P=0.018). HGF plasmid also improved QOL. There were no major safety problems. HGF gene therapy is safe and effective for CLI.

[Radical surgery using modified open door method for anterior apical tumor].

The approach that should be used for an anterior apical tumor still remains controversial. Since a modified open door method was very useful for the widening of the surgical field in a recent patient with an anterior apical tumor, an outline of this case is reported. The patient was a 66-year-old male with squamous cell carcinoma of the anterior apical region of the right lung (suspected to be invading the thoracic wall, cT3N1M0). After a midline sternal incision with a right unilateral collar incision, the medial half of the right clavicle and a few cm of the right 1st rib on the sternal side were resected to sufficiently expose the area from the right brachiocephalic trunk to around the subclavicular artery and vein, where invasion was suspected. This treatment facilitated widening of the visual field around the site of tumor invasion and made safe right upper lobectomy + combined thoracic wall resection + ND2a possible. In this patient, anterolateral incision at the 4th intercostal level, which is made using the original open door method, could be avoided, probably minimizing surgical invasion.

[Solitary fibrous tumor of the visceral pleura being suspected of chest wall origin: report of a case].

We report a case of a solitary fibrous tumor (SFT) of the pleura which is suspected of chest wall tumor. A 52-year-old female was admitted to our hospital because of epigastralgia and body weight loss. Chest X-ray and computed tomography showed a circumscribed mass of 35 x 22 mm in diameter arising from the parietal pleura. Positron emission tomography showed uptake valve of 1.5. SFT of chest wall origin was suspected and performed video-assisted thoracic surgery. The pedunculated tumor attached to the visceral pleura. The tumor was diagnosed as a benign SFT in intraoperative diagnosis. Long term clinical follow-up is recommended for patients with SFT, because the tumor recurrence and malignant transformation may occur in tumors with benign histological features.

Evaluation of the flow characteristics of an internal thoracic artery graft after coronary artery bypass grafting by intercostal Duplex scanning ultrasonography.

AIM: We previously reported intercostal duplex scanning ultrasonography to be a reliable technique for the evaluation of the internal thoracic artery (ITA). The purpose of this study was to determine the flow characteristics of the ITA graft using this technique. METHODS: We evaluated the flow characteristics of 69 ITA grafts who underwent coronary artery bypass grafting by this technique. The internal diameter, mean systolic and diastolic velocity, total flow volume and diastolic fraction were all thus obtained. RESULTS: One occluded graft was found during the follow-up. The mean systolic velocity significantly decreased after the operation (P=0.0001) and the mean diastolic velocity significantly increased both just after the operation (P=0.0002) and 1 year later (P=0.0283). The average diameter of the ITA graft after the operation (1.70+/-0.39), at 1 year (1.73+/-0.29) and at 2 years thereafter (1.66+/-0.27 mm) all significantly decreased in comparison to the preoperative value (2.30+/-0.35 mm) (P=0.0001). The average total flow volume after the operation (35.8+/-22.2), and at 1 year (29.4+/-16.5) and 2 years thereafter (23.4+/-12.7), respectively, were significantly decreased in comparison to the preoperative value (59.4+/-28.6 mL/min) (P=0.0001). However, the average diastolic fraction which was 25.1+/-10.5% before the operation significantly increased after the operation (54.5+/-12.0, 53.2+/-11.2 at 1 year and 50.4+/-9.3 at 2 years) (P=0.0001). CONCLUSION: This technique is thus considered to be a useful noninvasive for the postoperative follow-up of the graft function. A significant increase in the diastolic fraction is thought to be important for maintaining long term graft patency.

Effect on vein graft intimal hyperplasia of nuclear factor-kB decoy transfection using the second generation of HVJ vector.

AIM: Vein graft stenosis due to intimal hyperplasia (IH) is the main cause of graft failure. We examined possibilities of nuclear factor-kB (NF-kB) expression in vein grafts, and inhibitive effects of NF-kB decoy on the gene expression and subsequent vein graft IH. METHODS: Fifteen mongrel dogs underwent femoral artery replacement with autogenous vein grafts. Group I: grafts were retrieved at a predetermined time and subjected to NF-kB binding activity assay; Groups II and III: grafts were transfected with scrambled (II-a, III-a) or NF-kB (II-b, III-b) decoy using hemagglutinating virus of Japan envelope before implantation. Grafts were retrieved 7 days after implantation for evaluation of intercellular adhesion molecule-1 (ICAM-1) mRNA expression (Group II) and 4 weeks after implantation for comparison of IH by morphometric analysis (Group III). RESULTS: NF-kB binding activity was increased in a time-dependent manner, with a peak 2 days after implantation. The ratio between ICAM-1 and glyceraldehyde-3-phosphate dehydrogenase mRNA expression in II-b was significantly lower than that in II-a (0.347 +/- 0.07 versus 0.612+/-0.08; P = 0.047). The ratio of intimal cross-section area to luminal cross-section area of III-b was significantly lower than that of the III-a (0.096+/-0.03 versus 0.461+/-0.11; P = 0.048). CONCLUSION: NF-kB binding activity in vein grafts increases after implantation, and transfection of NF-kB decoy before implantation may reduce IH through the inhibition of ICAM-1 expression.

[Solitary fibrous tumor of the pleura; report of a case].

An 81-year-old male appealed against a feeling of dyspnea, and consulted the hospital. The giant tumor discovered in the thorax and it was enlarging gradually for 7 years. The tumor shadow with a diameter of about 15 cm was noted in right lower lung field on the chest X-ray. A definite diagnosis was not obtained by the needle biopsy. The tumor was found to exist between upper lobe and lower lobe and pressed lower lobe at surgery. The tumor was completely excised with partial resection of the collapsed lower lobe. The tumor was 1,050 g in weight and 18 cm in maximum diameter. Pathological examination showed the irregular and plan-like arrangement of the spindle-shape cell. Immunohistochemical study revealed positive findings for bcl-2 and CD34, negative findings for desmin, ketatin, and alpha-actin. The tumor was diagnosed as malignant solitary fibrous tumor of the pleura due to highly atypical nuclear finding with an abundant nuclear fission or histology.

[Vacuum-assisted wound closure in the management of deep sternal wound infection].

We herein present a case who underwent vacuum-assisted wound closure (VAC) therapy for post-sternotomy mediastinitis. A 71-year-old female with chronic renal failure on dialysis underwent a graft replacement of the ascending aortic aorta for the treatment of an acute aortic dissection. After she was discharged from the hospital, a purulent discharge was noted to occur from the median sternal wound. The wound was therefore reopened and all sternal wires were removed. Thereafter, polyurethane foam which was shaped to fit the defect was placed within the cavity. The area was covered with adhesive drape and suction drainage was carried out at -100 mmHg. The polyurethane foam was replaced every few days. The wound was finally closed using a muscle flap at 49 days after surgery. VAC therapy is therefore considered to be a useful treatment modality for deep sternal wound infections.

Tumor growth modulation by sense and antisense vascular endothelial growth factor gene expression: effects on angiogenesis, vascular permeability, blood volume, blood flow, fluorodeoxyglucose uptake, and proliferation of human melanoma intracerebral xenografts.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, has been investigated as a potent mediator of brain tumor angiogenesis and tumor growth. We evaluated the effect of VEGF expression on the pathophysiology of tumor growth in the brain. Human SK-MEL-2 melanoma cells, with minimal VEGF expression, were stably transfected with either sense or antisense mouse VEGF cDNA and used to produce intracerebral xenografts. Vascular permeability, blood volume, blood flow, and tumor fluorodeoxyglucose metabolism were assessed using tissue sampling and quantitative autoradiography. Tumor proliferation was assessed by measuring bromodeoxyuridine labeling indices. Tumor vascular density and morphological status of the blood-brain barrier were evaluated by immunohistochemistry. SK-MEL-2 cells transfected with sense VEGF (V+) expressed large amounts of mouse and human VEGF protein; V+ cells formed well-vascularized, rapidly growing tumors with minimal tumor necrosis. V+ tumors had substantial and significant increases in blood volume, blood flow, vascular permeability, and fluorodeoxyglucose metabolism compared to wild-type and/or V- (antisense VEGF) tumors. VEGF antisense transfected V- expressed no detectable VEGF protein and formed minimally vascularized tumors. V- tumors had a very low initial growth rate with central necrosis; blood volume, blood flow, vascular permeability, and glucose metabolism levels were low compared to wild-type and V+ tumors. A substantial inhibition of intracerebral tumor growth, as well as a decrease in tumor vascularity, blood flow, and vascular permeability may be achieved by down-regulation of endogenous VEGF expression in tumor tissue. VEGF-targeted antiangiogenic gene therapy could be an effective component of a combined strategy to treat VEGF-producing brain tumors.

Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography.

We report a series of studies that assess the feasibility and sensitivity of imaging of herpes virus type one thymidine kinase (HSV1-tk) gene transfer and expression with [124I]-5-iodo-2'-fluoro-1-beta-D-arabinofuranosyluracil ([124I]-FIAU) and positron emission tomography (PET) and the ability of [124I]-FIAU-PET imaging to discriminate different levels of HSV1-tk gene expression. Studies were performed in rats bearing multiple s.c. tumors derived from W256 rat carcinoma and RG2 rat glioma cells. In the first set, we tested the sensitivity of [124I]-FIAU-PET imaging to detect low levels of HSV1-tk gene expression after retroviral-mediated gene transfer. HSV1-tk gene transduction of one of preestablished wild-type W256 tumor in each animal was accomplished by direct intratumoral injection of retroviral vector-producer cells (W256-->W256TK* tumors). Tumors produced from W256 and W256TK+ cells served as the negative and positive control in each animal. Highly specific images of [124I]-FIAU-derived radioactivity were obtained in W256TK* tumors (that were transduced in vivo) and in W256TK+ tumors but not in nontransduced wild-type W256 tumors. The level of "specific" incorporated radioactivity in transduced portions of both W256TK* and W256TK+ tumors was relatively constant between 4 and 50 h. In the second set, we tested whether [124I]-FIAU and PET imaging can measure and discriminate between different levels of HSV1-tk gene expression. Multiple s.c. tumors were produced from wild-type RG2 cells and stably transduced RG2TK cell lines that express different levels of HSV1-tk. A highly significant relationship between the level of [124I]-FIAU accumulation [% injected dose/g and incorporation constant (Ki)] and an independent measure of HSV1-tk expression (sensitivity of the transduced tumor cells to ganciclovir, IC50) was demonstrated, and the slope of this relationship was defined as a sensitivity index. We have demonstrated for the first time that highly specific noninvasive images of HSV1-tk expression in experimental animal tumors can be obtained using radiolabeled 2'-fluoro-nucleoside [124I]-FIAU and a clinical PET system. The ability to image the location (distribution) of gene expression and the level of expression over time provides new and useful information for monitoring clinical gene therapy protocols in the future.

Long-term positron emission tomography evaluation of slowly progressive gliomas.

Non-invasive positron emission tomography (PET) was performed to identify changes in blood flow and metabolism, specific to early stages of tumour occurrence or recurrence. 2 patients with slowly progressive gliomas from early to late stages of tumour development were analysed by serial PET measurements of circulation and metabolism using 15O-gas and 18F-fluorodeoxyglucose. PET revealed a persistent depression of oxygen metabolism, as indicated by the regional oxygen extraction fraction or metabolic rate of oxygen, in the regions where tumours were later found. Abnormal blood flow and metabolism may precede the morphological changes detected by computed tomography (CT) in patients with gliomas.

Innovative approach in the diagnosis of gliomatosis cerebri using carbon-11-L-methionine positron emission tomography.

A case of gliomatosis cerebri was studied with positron emission tomography (PET). Carbon-11-L-methionine (11C-Met) accumulated in the diffusely infiltrative tumorous area more widely and accurately than the lesion detected by conventional x-ray computerized tomography (CT) or magnetic resonance (MR) imaging. Autopsy findings three months after the time of the PET study showed good anatomical correspondence between the extent of densely aggregated tumor cells and the region with high uptake of 11C-Met. PET may offer an innovative approach in the delineation of gliomatosis cerebri, which has not been clearly recognized by CT or MR.

Effect of a serotonin receptor antagonist on interleukin-6-induced pulmonary hypertension in rats.

STUDY OBJECTIVES: To determine the significance of serotonin in the pathogenesis of interleukin (IL) 6-induced pulmonary hypertension (IL-6-PH) in rats, the plasma serotonin concentrations, and the effects of a specific antagonist of the serotonin (5-hydroxytryptamine [5-HT]) receptor, 1-[o-(m-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2-propyl hydrogen succinate hydrochloride (MCI) on the degree of pulmonary hypertension (PH) were investigated in MCI-treated IL-6-PH (IL-6-MCI-PH) rats. MEASUREMENTS: The thickness of the media of small pulmonary arteries and the ratio of the weight of the right ventricle free wall (RV) to that of the left ventricle with the septum (LV + S) were measured as indexes of the degree of PH. Serotonin concentrations in plasma and in supernatants of cultured vascular smooth muscle cells (VSMCs) stimulated by IL-6 were measured by high-performance liquid chromatography. The amplification of DNA encoding the 5-HT receptor in the lung specimen and VSMCs was performed by polymerase chain reaction. RESULTS: The degree of PH, as determined by the medial thickness of small pulmonary arteries, was significantly increased in IL-6-PH rats as compared with normal control rats (p<0.05), and that in IL-6-MCI-PH rats was not significantly different from that in normal control rats. The RV/LV + S weight ratio in the IL-6-PH rats was significantly higher than that in normal control rats (p < 0.01). The RV/LV + S weight ratio in IL-6-MCI-PH rats was significantly lower than that in IL-6-PH rats (p < 0.01) and was not significantly different from that in normal control rats. The serotonin concentration was significantly higher in IL-6-PH rats than in normal control rats (p < 0.02), and the serotonin concentration in IL-6-MCI-PH rats was not significantly different from that in the normal control rats. The expression levels of the 5-HT receptor messenger RNA in the lung tissue tended to increase in IL-6-PH rats but was suppressed in IL-6-MCI-PH rats. IL-6 significantly increased the amount of serotonin released from VSMCs (p < 0.02). The expression of the 5-HT receptor messenger RNA was observed with IL-6 stimulation as was observed with serotonin stimulation in VSMCs. CONCLUSIONS: Serotonin receptor antagonists could be considered as potentially useful agents for the treatment of chronic thromboembolic PH, as well as for that of primary PH and PH associated with collagen vascular diseases.

Konno procedure for infective endocarditis involving aortic valve in a small child.

The Konno procedure was performed to replace the aortic valve and the sinus of Valsalva in a 1-year-old child with pneumococcal infective endocarditis. A Dacron (C.R. Bard, Haverhill, PA) graft and a 16 AP ATS Medical valve (ATS Medical Inc, Minneapolis, MN) were used. Adequate debridement could be easily performed. Postoperative recovery was uneventful. The procedure, originally developed for a narrow aortic annulus, could be a good option for the treatment of a small child with aortic valve endocarditis.

Tube device for facilitating distal anastomosis in aortic arch replacement.

The technique of placing an inverted graft into the descending thoracic aorta facilitates and secures the distal anastomosis in aortic arch replacement, especially in the anastomosis beyond the transverse arch. We developed a simple technique using a pair of thin-walled tubes to enable the arch graft, with its four branches, to be smoothly inserted into the flaccid, normal-caliber descending aorta. The use of these tubes simplified the procedure, resulting in time saving.

Vascular clamp for hemostasis and stabilization during minimally invasive direct coronary artery bypass.

A soft vascular clamp was used for hemostasis and stabilization of the operative field during minimally invasive direct coronary artery bypass (MIDCAB). The instrument was gently applied so that it clamps the coronary artery by grasping the adjacent myocardium. The method offered dry and stable operative field without a special instrument or technique. The surgical results have been satisfactory. We found application of the vascular clamp to be very helpful for MIDCAB.

Anastomotic complications after bronchoplastic procedures for nonsmall cell lung cancer.

BACKGROUND: Anastomotic complications associated with bronchoplastic procedures cannot be completely avoided despite the improvements made in surgical techniques and suture materials. Thus, the present study attempted to clearly define the significant factors influencing anastomotic complications. METHODS: Between 1978 and 1998, 47 patients with primary nonsmall cell lung cancer underwent bronchoplastic procedures. The incidences of anastomotic complications were calculated according to each of the following clinical factors: primary site, age, pathologic type, pT factor, pN factor, pulmonary arterioplasty, surgical procedure, suture material, coverage of the anastomotic line, positive resection margin, and preoperative chemotherapy. The results were analyzed using univariate and multiple logistic regression analysis. RESULTS: Anastomotic complications occurred in 8 patients. Four had anastomotic dehiscence and 4 had stenosis. Of these 8 patients, the resection margin was diagnosed as being positive in 6 patients. Three showed metastasis of the most distal mediastinal lymph node whereas the others had a residual tumor at the bronchial resection margin. According to multiple logistic regression analysis, only pN factor (p = 0.04) and positive resection margin (p = 0.02) had a significant influence on the complications. CONCLUSIONS: Thus, pN2 patients, especially those with metastasis of the most distal mediastinal lymph node and patients with a residual tumor at the bronchial resection margin, have a significantly higher risk of anastomotic complications.

Morphology and histology of human and canine internal thoracic arteries.

BACKGROUND: We evaluated human and canine internal thoracic arteries (ITAs) to determine whether the latter is valid for studies relevant to clinical use. METHODS: We studied 19 human ITAs obtained from 1 female and 14 male victims of recent fatal accidents who had no evidence of cardiovascular disease (mean age = 39+/-19 years; range = 15 to 79 years), and ITAs of 21 randomly-selected mongrel dogs of both sexes, weighing 18-40 kg (average = 24.3+/-5.7 kg). Specimens were fixed in formalin at a controlled pressure of 120 mm Hg, before extensive assessment that included intimal thickening, condition of the internal elastic lamina, and number of medial elastic lamellae and vasa vasorum. RESULTS: The canine morphology and histology were similar to the human ITAs, but there was no intimal hyperplasia, and the media and adventitia were thinner (ITAs of humans older than 40 years had significant increases in medial thickness, as well as in overall length). Morphologically and histologically, the left and right canine ITAs were almost completely the same. CONCLUSIONS: Canine ITAs are valid for bilateral comparative studies and are a useful tissue source and model for clinically-relevant experimental studies.