Motoshi Takao

Percutaneous Radiofrequency Ablation of Lung Neoplasms: Initial Therapeutic Response

PURPOSE To evaluate the feasibility, safety, and initial therapeutic effect of radiofrequency (RF) ablation in the treatment of unresectable malignant lung tumors. MATERIALS AND METHODS Fifty-four lung neoplasms in 31 patients were treated with RF ablation. Thirteen tumors were primary lung cancers and 41 were pulmonary metastases. Tumor sizes ranged from 0.7 to 6.0 cm, with a mean size of 2.7 +/- 1.3 cm. After the RF electrode was placed in the tumor with computed tomographic (CT) fluoroscopic guidance, RF energy was applied. Initial therapeutic response was evaluated by (18) F fluorodeoxyglucose positron emission tomography (FDG-PET) and contrast-enhanced CT. The disappearance of FDG uptake on PET images and tumor enhancement on CT images were considered to indicate complete tumor necrosis. Complete necrosis rates were evaluated according to tumor size and type (primary or secondary lung neoplasm). RESULTS RF ablation was technically successful in all lesions. Complete necrosis was achieved in 32 of the 54 tumors (59%) after initial RF session. There was a significant difference in the rate of complete tumor necrosis between tumors 3 cm or less and tumors larger than 3 cm (69% vs. 39%; P <.05). Tumor type did not influence complete necrosis rates. Lung abscesses developed in two patients with large tumors. CONCLUSION Lung RF ablation is a feasible, relatively safe, and promising treatment for unresectable lung neoplasms. Tumor size is an important factor in achieving complete tumor necrosis.

Alterations in coagulation and fibrinolysis associated with cardiopulmonary bypass during open heart surgery

The effect of heparin as an anticoagulant was examined and the extent of fibrinolytic activity during cardiopulmonary bypass (CPB) was measured. Twenty patients undergoing valve replacement or aortocoronary bypass surgery were studied. Fibrinopeptide A (FPA) levels gradually became elevated as CPB proceeded, and antithrombin III (AT III) decreased during CPB. This indicates that despite the use of heparin, the coagulation system was activated, leading to fibrin formation in the microcirculation. On the other hand, fibrinopeptide B (FPB beta 15-42) also increased to four times the preoperative value at two hours on CPB. Intrinsic fibrinolytic activity, as determined by the activity of kaolin-activated euglobulin, was transiently increased only at the beginning of CPB. The C1 inactivator-resistant fibrinolytic activity and tissue plasminogen activator antigen (t-PA;Ag) increased sharply during CPB and reached maximum levels one hour after the start of CPB, indicating that enhanced fibrinolytic activity during CPB is predominantly of extrinsic origin as the result of t-PA release from the vascular walls. It is concluded from the above findings that thrombin activity continues during CPB. Enhanced fibrinolytic activity during CPB appears to be important because t-PA activates plasminogen predominantly where fibrin is formed, leading to dissolution of the microthrombi formed during CPB.

Long-Term Follow-up After Carpentier-Edwards Ring Annuloplasty for Tricuspid Regurgitation

BACKGROUND Use of flexible rings for tricuspid ring annuloplasty is becoming popular. This study was undertaken to evaluate Carpentier-Edwards (C-E) rigid ring annuloplasty for tricuspid regurgitation (TR), secondary to mitral valve disease and clinical outcome on a long-term basis. METHODS From December 1985 to March 1996, 45 patients with secondary TR underwent C-E ring annuloplasty. Thirty-nine patients (95.1%) were in New York Heart Association (NYHA) functional class III or IV. The mean follow-up was 96.7+/-48.5 months or 362.6 patient-years. RESULTS There were three in-hospital and nine late deaths that were not related to tricuspid annuloplasty. Actuarial survival at 10 years was 68.3%. Echocardiographic studies showed that TR was well controlled within grade 2+ in all survivors. Residual pulmonary hypertension (PH) was recognized in 9 of 21 patients (42.9%) with preoperative PH, however, no TR was seen in 6 patients. A TR grade of 2+ was observed in 3 patients. Thirty of the total survivors (96.8%) were in NYHA class I and II, but 1 patient was in NYHA class III. The actuarial rate of freedom from tricuspid valve reoperation after 10 years was 97.5%. CONCLUSIONS C-E ring annuloplasty is acceptable for repair of secondary TR and improvement in clinical status on a long-term basis.

Assessment of factors influencing FDG uptake in non-small cell lung cancer on PET/CT by investigating histological differences in expression of glucose transporters 1 and 3 and tumour size

PURPOSE The objective of this study was to evaluate the major factors influencing on FDG uptake in non-small cell lung cancer (NSCLC) by investigating histological difference in the expression of glucose transporters 1 and 3 (Glut-1 and Glut-3) and tumour size. METHODS This study enrolled 32 patients including 9 with squamous cell carcinoma (SCC) and 23 with adenocarcinoma (AC). The AC cases comprised 16 AC with mixed subtypes (AC-mixed) and 7 localized AC in situ (localized bronchioloalveolar carcinoma). Partial volume effect corrected maximum standardized uptake values (cSUVmax) and tumour size were obtained using FDG PET/CT. Glut-1 and Glut-3 expression were evaluated using five-point grading scales. RESULTS Overexpression of Gluts was observed at high rates (88% for Glut-1 and 97% for Glut-3). They were mutually correlated. cSUVmax showed better correlation with size than with Gluts overexpression. AC and SCC showed a high positive expression rate for both Glut-1 and Glut-3, although the degree of overexpression was significantly higher in SCC than AC. In addition, localized AC in situ revealed a considerably higher positive expression rate and similar degrees of overexpression for both Glut-1 and Glut-3 compared with AC-mixed. By contrast, localized AC in situ alone was significantly smaller in both cSUVmax and size than either SCC or AC-mixed. No significant difference was found in cSUVmax or size between SCC and AC-mixed. CONCLUSIONS The FDG uptake of NSCLC might be dependent on size rather than on overexpression of Glut-1 or Glut-3. Low FDG uptake in localized AC in situ might result from its small size rather than Glut overexpression.

Silicone-coated polypropylene hollow-fiber oxygenator : Experimental evaluation and preliminary clinical use

BACKGROUND A membrane oxygenator consisting of a microporous polypropylene hollow fiber with a 0.2-microm ultrathin silicone layer (cyclosiloxane) was developed. Animal experimental and preliminary clinical studies evaluated its reliability in bypass procedures. METHODS Five 24-hour venoarterial bypass periods were conducted on dogs using the oxygenator (group A). In 5 controls, bypass periods were conducted using the same oxygenator without silicone coating (group B). As a preliminary clinical study, 14 patients underwent cardiopulmonary bypass with the silicone-coated oxygenator. RESULTS Eight to 16 hours (mean, 12.2 hours) after initiation of bypass, plasma leakage occurred in all group B animals, but none in group A. The O2 and CO2 transfer rates after 24 hours in group A were significantly higher than at termination of bypass in group B (p < 0.005 and p < 0.03, respectively). Scanning electron microscopy of silicone-coated fibers after 24 hours of bypass revealed no damage to the silicone coating of the polypropylene hollow fibers. In the clinical study, the oxygenator showed good gas transfer, acceptable pressure loss, low hemolysis, and good durability. CONCLUSIONS This oxygenator is more durable and offers greater gas transfer capabilities than the previous generation of oxygenators.

Pulmonary leiomyosarcoma extending into left atrium or pulmonary trunk: complete resection with cardiopulmonary bypass☆☆☆★★★

Primary pulmonary leiomyosarcoma is a rare tumor. Few cases have been treated surgically because of its rapid invasion into the pulmonary trunk or heart and tendency toward massive intrapulmonary metastases. We report the cases of two patients with leiomyosarcoma originating in a pulmonary artery or vein that involved the pulmonary trunk or left atrium, both of whom underwent complete surgical resection with cardiopulmonary bypass (CPB). Since their operations, these patients have shown no evidence of recurrent tumor. PATIENT 1. A 72-year-old woman with persistent cough, chest pain, and hemoptysis was referred to our hospital for evaluation and treatment of presumed pulmonary thromboembolism. An angiogram revealed filling defects in the pulmonary trunk, absence of filling of the left main pulmonary artery, and decreased arterial filling in the left lung. A biopsy specimen was obtained from a tumor in the left main pulmonary artery by means of a suction catheter, and the pathologic diagnosis of sarcoma was made. Computed tomography disclosed a mass occluding the left main pulmonary artery and densely filling pulmonary artery branches. Median sternotomy was performed and CPB was applied. The left pulmonary veins were ligated and the left main pulmonary artery was incised. A large tumor completely filled the left main pulmonary artery. Extension of the incision into the pulmonary trunk disclosed that the tumor invaded its wall laterally on the left. The portion of tumor located in the left main pulmonary artery and pulmonary trunk, including the left main pulmonary artery and the left lateral wall of the trunk, was excised. Direct suture closure of the pulmonary trunk was carried out and CPB was terminated. The left main bronchus was transected and left pneumonectomy was completed. Fig. 1 shows the resected left lung and pulmonary artery. Tumor in the main pulmonary artery extended intraluminally into its branches. The tumor was diagnosed histologically with the aid of immunohistochemical stainFrom the Department of Thoracic and Cardiovascular Surgery, Mie University, School of Medicine, Tsu, Japan.

Ultrafiltration of the priming blood before cardiopulmonary bypass attenuates inflammatory response and improves postoperative clinical course in pediatric patients.

ABSTRACT The priming solution using in cardiopulmonary bypass (CPB) for infants undergoing cardiac surgery includes considerable amounts of stored blood. Our objective was to test the hypothesis that ultrafiltration (UF) of the stored blood before CPB reduces the unfavorable effects of stored blood and the production of inflammatory cytokines. Fifty pediatric patients with congenital heart defects took part in this study. The patients were randomly divided into two groups: the UF (27 pediatric patients who received UF) and control (23 pediatric patients who did not receive UF) groups. UF was performed with a polysulphone ultrafiltrator before CPB. Blood samples were collected immediately before, during, and 1 h after CPB. The levels of cytokines (TNF‐&agr;, IL‐1&bgr;, IL‐8), NH3, and bradykinin were determined. The serum concentrations of NH3 and bradykinin decreased significantly after UF. Compared with the control group, the UF group had significantly lower cytokine production. Water balance in UF group was better than that of control group. The UF group received significantly less inotropic support and shorter duration of ventilator support and ICU stay. We conclude that removal of bradykinin and a decrease in the levels of NH3, potassium, and pH play a significant role in reducing water retention and postoperative lung injury. UF of the blood used to prime the circuit for CPB is a safe and efficient method for use in open heart surgery in small pediatric patients.

Biocompatibility of silicone-coated oxygenator in cardiopulmonary bypass

BACKGROUND This study was designed to analyze the biocompatibility of silicone-coated oxygenators using inflammatory response as the outcome measure, and to investigate whether the silicone-coated oxygenators perform better in terms of postoperative organ dysfunction. METHODS The 32 patients who underwent cardiopulmonary bypass (CPB) were divided into 3 groups: group A (n = 10), heparin-coated circuit with silicone-coated oxygenator; group B (n = 11), whole heparin-coated circuit; and group C (n = 11), whole untreated circuit. The plasma concentrations of the proinflammatory markers, made of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-8), terminal complement complex (C5b-9), and polymorphonuclear elastase (PMN-E), were measured by enzyme-linked immunosorbant assay. RESULTS All proinflammatory markers were significantly lower in groups A and B than in group C, especially C5b-9 and PMN-E concentrations, which were significantly lower in group A than in group B. The alveolar-arterial oxygen gradients (A-aDO2) and the respiratory index were significantly better in group A than in group C. In group B, however, only the A-aDO2 was significantly better than in group C. The duration of intubation and the length of stay in the intensive care unit stay were significantly shorter in groups A and B than in group C. CONCLUSIONS Silicone-coated oxygenators are biocompatible and prevent postoperative organ dysfunction.

Tumor Seeding Following Lung Radiofrequency Ablation: A Case Report

Lung radiofrequency (RF) ablation was performed for the treatment of a primary lung cancer measuring 2.5 cm in maximum diameter in a 78-year-old man. A contrast-enhanced computed tomography (CT) study performed 3 months after RF ablation showed incomplete ablation of the lung tumor and the appearance of a chest wall tumor 4.0 cm in maximum diameter that was considered to be the result of needle-tract seeding. RF ablation was performed for the treatment of both the lung and the chest wall tumors. Although tumor enhancement was eradicated in both of the treated tumors, follow-up CT studies revealed diffuse intra-pulmonary metastases in both lungs 2 months after the second RF session. He is currently receiving systemic chemotherapy.

Immunohistochemical diagnosis of methylthioadenosine phosphorylase (MTAP) deficiency in non-small cell lung carcinoma

Methylthioadenosine phosphorylase (MTAP) is involved in the metabolism of purines and converts methylthioadenosine (MTA) to adenine. It is abundant in all normal tissues but is deficient in various tumors. Here, we investigated MTAP deficiency in clinical samples of lung cancer using immunohistochemistry (IHC), and compared these results with those obtained by real-time PCR. Seventy-five samples were obtained from patients who underwent operations for non-small cell lung cancer (NSCLC). MTAP genetic analysis, using real-time PCR, and IHC were carried out on the samples. Methylation-specific primers were used to analyze methylation of the MTAP promoter, using DNA treated with sodium bisulfite. Sixty-nine of 75 samples were compared using both IHC and real-time PCR. The IHC results were consistent with those of real-time PCR in 56 samples. Of 62 positive samples tested by real-time PCR, only 49 (79%) were MTAP-positive by IHC. Seven samples were MTAP-negative by real-time PCR and IHC. In 13 samples of PCR (+) and IHC (-), six samples showed that the promoter region of MTAP was methylated. IHC is an accurate and useful diagnostic method for detecting MTAP deficiency in NSCLC, and the frequency of MTAP deficiency was found to be relatively high. The metabolic alterations diagnosed by IHC could be exploited for selective chemotherapy.