High serum levels of procollagen type III N-terminal amino peptide in patients with congenital heart disease.

OBJECTIVE: The serum concentration of aminoterminal procollagen type III (PIIIP) is considered a useful marker of tissue fibrogenesis. The present study tested the hypothesis that: serum PIIIP levels are elevated in patients with congenital heart disease (CHD) and abnormal haemodynamic loading and/or hypoxaemia; PIIIP levels are associated with the severity of haemodynamic load or hypoxaemia, both of which enhance myocardial fibrosis. METHODS AND RESULTS: Serum PIIIP levels were measured in five groups of CHD patients (42 patients with ventricular septal defect (VSD), 26 with coarctation of the aorta (COA, n = 19) or aortic stenosis (AS, n = 7), 36 with atrial septal defect (ASD), 39 with pulmonary stenosis (PS) and 20 with tetralogy of Fallot (TOF)). PIIIP levels of CHD patients were significantly higher than those of 42 control subjects (p<0.05, each). Serum PIIIP levels increased in parallel with increased ventricular volume load in VSD and ASD, and with the severity of PS. In TOF patients, PIIIP levels correlated negatively with arterial oxygen saturation. Treatment with an angiotensin-converting enzyme inhibitor (ACEI) was associated with low levels of PIIIP in COA/AS patients despite the existing haemodynamic load. CONCLUSION: The increased serum PIIIP levels in proportion to the severity of ventricular load or cyanosis suggest enhanced myocardial synthesis of collagen type III in patients with CHD. Suppression of the PIIIP level by ACEI suggests the involvement of the renin-angiotensin-aldosterone system in myocardial fibrosis. These data provide the basis for the development of new diagnostic and therapeutic strategies in patients with CHD.

[Gastrointestinal hemorrhage induced by percussive ventilator in an infant with chronic lung disease complicated after surgery for corrected transposition of the great arteries].

A newborn patient (birth weight 2,332 g) with corrected transposition of the great arteries developed chronic lung disease due to a severe heart failure and post operative several complications. We applied intrapulmonary percussive ventilation (IPV) to the patient. IPV improved oxygenation concomitant with the improvement of respiratory condition and chest X-ray finding. However, the patient suffered from upper gastrointestinal bleeding 15 days after initiation of IPV therapy. The bleeding was healed several days after temporal termination of IPV, but recurred with resuming IPV therapy. The patient was irritable throughout the IPV therapy, and thus gastrointestinal bleeding of the patient could be due to stress induced by IPV therapy. IPV may be useful for the management of respiratory disturbance, often observed in low birth weight patients with congenital heart defects. However, gastrointestinal bleeding may occur and should be considered as a possible complication associated with IPV therapy.

Efficacy and safety of torasemide in children with heart failure.

OBJECTIVE: To examine the efficacy and safety of torasemide in children with chronic heart failure (HF). METHODS: 102 children with chronic HF who had received oral torasemide were analysed. Of these, 62 (de novo group) were newly diagnosed as having HF and were given torasemide as a diuretic. The remaining 40 (replacement group) had been given furosemide for >3 months before the study, and furosemide was then replaced with torasemide. Clinical signs and symptoms of HF (assessed as the HF index), humoral factors and serum potassium concentrations before torasemide treatment were compared with those obtained 3-4 weeks after torasemide treatment. Patients were also monitored for adverse effects. RESULTS: In the de novo group, torasemide significantly improved the HF index with concomitant improvement in plasma brain natriuretic peptide concentration (median (interquartile range) 52 (51) vs 43 (49) pg/ml). In a randomly selected group of 25 de novo patients with ventricular septal defect, echocardiography showed that torasemide significantly improved left ventricular geometry and function. In the replacement group, brain natriuretic peptide concentrations were also significantly decreased from 50 (104) to 45 (71) pg/ml after substitution of torasemide, but the HF index showed only a tendency for improvement (p = 0.07). Torasemide also had a potassium-sparing effect (de novo group, no change in potassium concentration; replacement group, significant increase from 4.2 (0.5) to 4.3 (0.5) mEq/l), and caused a significant rise in serum aldosterone concentration, consistent with the anti-aldosterone effect of this drug. Serum concentrations of sodium and uric acid had not changed after torasemide treatment, and there were no serious adverse events that necessitated drug withdrawal. CONCLUSION: Torasemide can be safely used, and appears to be effective for treatment of HF in children. Future clinical trials are warranted to verify the present results.

[Anomalous systemic arterial supply to the basal segment of the left lung; report of a case].

A 35-year-old female was admitted to our hospital for hysteromyoma. Chest X-ray showed a mass shadow in the left lung field. A thorough examination revealed anomalous systemic arterial supply to the basal segment of the left lung with 2 abnormal arteries. Because the patient had no symptoms, no operation was performed. After 9 months however, the patient had bloody phlegm and chest pain and received an operation. Thus, we propose that the operation for the pulmonary sequestration is to be performed when such a diagnosis is made.

[The significance of neoadjuvant intra-arterial chemotherapy for locally advanced breast cancer by different methods].

For neoadjuvant intra-arterial (IA) chemotherapy in locally advanced breast cancer patients, Seldinger's methods were found to be convenient and had the same effect and outcome as conventional methods. The prognosis of the patients in whom IA chemotherapy was locally effective and had fewer than n 1 lymph node metastases was comparatively favorable. However, several patients who underwent IA chemotherapy later experienced local recurrence, and the cause of these patient's death was distant metastases in almost all cases. We recommend neoadjuvant IA and systemic chemotherapy, and systemic adjuvant chemotherapy.

[Brain infarction related to hepatic arterial infusion chemotherapy].

We examined the occurrence of brain infarction with hepatic arterial infusion chemotherapy for liver cancer. One hundred and eighty-one cases of hepatic arterial infusion chemotherapy were carried out for liver cancer patients in 4 hospitals associated with Osaka University 2nd Dept. of Surgery. These included metastatic (n = 103) and primary (n = 78) liver tumors. The medication was mainly 5-FU with/without CDDP and IFN. Catheters were inserted via the left subclavian artery in 106 cases and via the femoral artery in 75 cases. Among these patients, brain infarctions occurred in seven patients. Occlusions were found in the cerebellum (n = 3), thalamus (n = 1), brain stem (n = 1) and TIA (n = 2). All these patients had catheterization from the left subclavian artery. Furthermore, 64 patients of Ikeda Municipal Hospital were examined and analyzed for brain infarction, in order to eliminate the difference between facilities (all patients in Ikeda Municipal Hospital were catheterized via the left subclavian artery). Many more brain infarctions occurred in metastatic liver cancer patients than in primary liver cancer patients. The hemostasis function deteriorated in primary liver cancer patients, and is thought to be involved in the brain infarction. Six of seven cases of brain infarction occurred in vertebral artery supply area. It may be that the occurrence of brain infarction was related to the flow of the blood vessels.

[A case of locally advanced breast cancer successfully treated with wide resection and reconstruction of chest wall with A-O metallic plates].

A 63-year-old female with locally advanced breast cancer was treated with preoperative chemotherapy using docetaxel. The therapeutic regimen was comprised of four cycles at 3-week intervals. One cycle consisted of 80 mg of docetaxel which was administered on day 1. A remarkable response was confirmed. The side effects such as leukopenia, general fatigue and alopecia were moderate and had no influence on the patient's QOL. After preoperative chemotherapy, a full thickness chest wall resection was performed. Chest wall defect was reconstructed with orthopedic A-O metallic plates, Marlex mesh and rectus abdominis myocutaneous flap. These metal plates were very useful because it was easy to bend and twist them manually to fit the defect at the time of operation. Moreover, the curved metal plates preserved the cone form of the chest cage. The postoperative course was favourable without frail chest or wound infection.

Assessment of cardiovascular dynamics by pressure-area relations in pediatric patients with congenital heart disease.

OBJECTIVES: It is particularly useful to separately quantify the ventricular contractility and loading conditions for a better understanding of the cardiovascular dynamics in congenital heart disease, where abnormalities in chamber and loading properties may coexist. Furthermore, ventricular contractility and loading conditions may alter independently or simultaneously with disease progression and therapeutic intervention. The objectives of the present study were (1) to test whether ventricular pressure-area analysis can provide such quantitation among patients with various forms of congenital heart disease, (2) to reveal basal cardiovascular interaction in congenital heart disease by means of pressure-area analysis, and (3) to test the feasibility of this method in a simplified and less invasive form to further enhance its clinical value. METHODS: We constructed pressure-area loops during caval occlusion by using transthoracic echocardiographic automated border detection combined with ventricular pressure recordings in 59 pediatric patients with congenital heart disease and in 7 normal control subjects. RESULTS: Area measurements obtained by automated border detection were highly reproducible, and area changes reflected volume changes. The pressure-area data provided load-independent measures of contractility, which were consistently increased by use of dobutamine (P <.05). End-systolic and arterial elastance individually quantified simultaneous changes in ventricular contractility and loading with milrinone infusion and predicted net cardiac performance. The pressure-area analysis better characterized the ventricular contractile states under a variety of loading conditions in congenital heart disease, whereas predominant load dependence of conventional indices confounded them. Furthermore, pressure-area relations were reasonably estimated from a single beat and from aortic pressure data during abdominal compression. CONCLUSIONS: Pressure-area analysis should provide a useful modality with which to assess cardiovascular dynamics in pediatric patients with congenital heart disease in more detail and should thus help improve the management of patients with this disease.

Circulating matrix metalloproteinases and their inhibitors in patients with Kawasaki disease.

BACKGROUND: Accelerated matrix breakdown caused by the increased activity of matrix metalloproteinases (MMPs) and/or the quantitative imbalance between MMP and tissue inhibitor of MMP (TIMP) have been implicated in several pathological conditions. MMP and TIMP may also be involved in the destruction of the coronary arterial wall and the resultant coronary arterial lesions in Kawasaki disease. METHODS AND RESULTS: Plasma levels of MMPs, neutrophil elastase, and TIMPs were measured by enzyme-linked immunoassay in 57 patients with Kawasaki disease and no coronary arterial lesions (group 1) and in 8 patients with Kawasaki disease and coronary arterial lesions (group 2). Blood samples were obtained before and after intravenous gamma globulin therapy and in the convalescent stage. Levels of MMPs, neutrophil elastase, and TIMPs were significantly higher in Kawasaki disease patients before gamma globulin therapy than in 18 age-matched afebrile control subjects and 17 age-matched febrile disease control subjects (P<0.01). More importantly, the pre-gamma globulin MMP9 level and MMP9/TIMP2 ratio and post-gamma globulin MMP3 level and MMP3/TIMP1 ratio were significantly higher in group 2 than in group 1 patients (P<0.05). Although MMP levels in febrile disease controls were significantly higher than those of afebrile controls, the MMP/TIMP ratios of febrile disease controls and afebrile controls were comparable. CONCLUSIONS: These data suggest that patients with Kawasaki disease and high levels of MMP and/or MMP/TIMP are susceptible to coronary arterial lesions. Studies of the effects of MMP inhibitors on coronary outcome may provide evidence that MMP is a viable therapeutic target for the prevention of coronary arterial lesions due to Kawasaki disease.

Inferior vena cava occlusion catheter for pediatric patients with heart disease: for more detailed cardiovascular assessments.

Traditional evaluation of cardiac function is too often limited by reliance on measurements with complex interdependence between cardiac properties and loading factors. Analysis by ventricular pressure-volume (P-V), -area (P-A), or -dimension (P-D) relations during inferior vena caval (IVC) occlusion independently quantifies ventricular properties and loading conditions, providing detailed information about cardiovascular dynamics. However, there has been no appropriate size of balloon catheter that can effectively occlude IVC of pediatric patients, hindering the application of P-V (P-A, or P-D) analysis to children with heart disease despite its potential benefit. To address this problem, we have developed a new balloon catheter for IVC occlusion in children. The catheter effectively occluded IVC in 92 pediatric patients with varying forms of heart disease who underwent cardiac catheterization, yielding end-systolic pressure-area relations. Thus a newly developed balloon catheter would contribute to establishing more accurate and detailed cardiovascular assessments in children with heart disease. Cathet Cardiovasc Intervent 2001;53:392-396.

Splenic and pulmonary metastases from renal cell carcinoma: report of a case.

We report herein the case of a patient in whom pulmonary and splenic metastases from renal cell carcinoma (RCC) were successfully treated by surgical excision. A 69-year-old man who underwent left nephrectomy for RCC 17 months before was suspected to have a pulmonary metastasis based on computed tomography (CT) findings. Partial resection of the left lower lobe was performed with thoracoscopic assistance. However, 4 months later, a splenic tumor, 6 cm in diameter, was detected by CT and ultrasonography, and a splenectomy was performed. Histologically, both resected specimens were diagnosed as metastasis from RCC. A second pulmonary metastasis of the left upper lobe was resected 4 years 8 months later. The patient was in good health when last seen 11 months after his last operation. Malignant neoplasms rarely metastasize to the spleen and most cases are found at autopsy, or feature multiple distant metastases. Only four other cases of splenic metastases from RCC have been reported. The prognosis associated with splenic metastasis is favorable when only a solitary lesion exists.

[Intra-arterial infusion therapy for unresectable liver metastasis of colorectal cancer].

Fifty-five colorectal carcinomas with metastatic liver tumor treated with intra-arterial 5-FU (> 5 g) infusion therapy at six hospitals were investigated retrospectively. The response rate reached 45%. The metastatic liver tumor from the rectum did not respond as well as that from the colon. Six patients could undergo liver resection and the infusion therapy was stopped in eleven patients due to a new extrahepatic lesion. The ratio of serum CEA levels of non-responders before infusion therapy and one month later was significantly higher and their survival period was shortened. This ratio indicated that this therapy could be continued.

[A case report of successful transcatheter arterial embolization therapy for osseous metastasis of hepatocellular carcinoma].

A 74-year-old man was admitted to our hospital with a chief complaint of severe local pain of the hip joint. Radiological findings showed a metastasized lesion on the left side of the pelvic wall originated from hepatocellular carcinoma (HCC) in the anterior segment of the liver. Transcatheter arterial embolization (TAE) therapy using epirubicin, Lipiodol and Spongel was successfully performed twice for primary HCC, and four times for osseous metastasis of HCC. After TAE therapy, the size of the metastasized lesion decreased with relief of pain, and an improvement in performance status of 4 to 2 was achieved. In conclusion, TAE therapy is thought to be very useful in the treatment of osseous metastasis of HCC with severe local pain.

[Intrapericardiac instillation of epirubicin for carcinomatous cardiac tamponade from breast cancer].

Three cases of carcinomatous cardiac tamponade from breast cancer are presented. All patients have had another recurrence and history of treatment. Though the prognoses were considered to be unfavorable, pericardiac drainage and the instillation of epirubicin were effective. Side effects of fever and dyspnea were experienced temporarily by two patients with no serious events. Following the systemic chemotherapy, two patients needed no supplemental drainage. All patients had a sufficient quality of life for about 1 year or longer. We found that positive therapy can be significant for such patients with advanced disease.

Total gastrectomy with dissection of lymph nodes along the splenic artery: a pancreas-preserving method.

BACKGROUND: In Japan, the tail and body of the pancreas are generally removed for dissection of lymph nodes along the splenic artery. A new pancreas-preserving method was developed to decrease the postoperative complications due to pancreatic resection. PATIENTS AND METHODS: Between 1981 and 1989, 110 patients were registered in a randomized controlled trial, which included total gastrectomy plus dissection of lymph node along the splenic artery, either with (55 patients: Group A) or without (55: Group B) pancreas tail resection. In Group B, the splenic artery and spleen were removed and the pancreas was preserved. There were no significant differences between the two groups in terms of sex, age, location, microscopic classification, or disease stage. The postoperative complications and survival rates were compared between the two groups. RESULTS: The average number of dissected nodes along the splenic artery was 4.6 and 4.1 for Groups A and B, respectively. The amounts of blood loss during the operation were 994 ml and 904 ml for groups A and B, respectively. Anastomosis failure and/or pancreatic fistula occurred in nine patients in Group A (16%) and seven in Group B (13%). One year after the operation, a glucose tolerance test showed diabetes in 6% and impaired glucose tolerance in 33% of patients in group A, while these findings were normal in group B. The 5-year survival rates were 80% and 76.7% for groups A and B, respectively. CONCLUSIONS: The pancreas-preserving method described here was superior to the more common pancreas resecting method with regard to surgical risk and postoperative glucose tolerance.

A case of breast cancer diagnosed by inguinal lymph node metastasis.

We describe a case of a 58-year-old woman with right inguinal lymph node swelling and a T1 tumor in the right breast. She was referred with an 18-month history of the former complaint and a six-month history of the latter. Excisional biopsy of the inguinal lymph node revealed breast cancer metastasis. Radiographical examination showed no metastases to the lungs, liver or bone. Modified radical mastectomy was performed. Histological examination revealed solid tubular carcinoma, PT2, PM (axillary lymph node metastases 4/16), stage IV. Estrogen and progesterone receptors were negative. Three cycles of postoperative cyclophosphamide, adriamycin and 5-fluorouracil (CAF) chemotherapy were given, and the right inguinal area was irradiated with 40 Gy. The patient complained of swelling in both legs three years after surgery. Computed tomography revealed marked lymph node swellings in the pelvic cavity. She died six months later. Inguinal lymph node metastasis from breast cancer is very rare, although distant lymph node metastasis in the cervix occurs frequently. This case should help clarify how breast cancer metastasizes to distant lymph nodes.