Altered p16/MTS1/CDKN2 and cyclin D1/PRAD-1 gene expression is associated with the prognosis of squamous cell carcinoma of the esophagus.

The p16/MTS1/CDKN2 gene and the cyclin D1/PRAD-1 gene cooperatively regulate cyclin-dependent kinase 4-mediated phosphorylation of pRB in the cell cycle of normal cells. p16/CDKN2 gene and cyclin D1/PRAD-1 gene alterations have been detected in squamous cell carcinoma cell lines and in several primary squamous cell carcinomas of the esophagus. We immunohistochemically assessed p16 and cyclin D1 expression in 111 squamous cell carcinomas of the esophagus after evaluation of the antibodies against p16 and cyclin D1 protein using four squamous cell carcinoma cell lines. Loss of p16 expression was detected in 56 of 111 cases (50%). The mean number of metastatic lymph nodes without p16 expression was significantly higher than the number of nodes with p16 expression (P = 0.04). The postoperative survival rate for patients without p16 expression was significantly lower than that of patients with p16 expression (P = 0.04). Cyclin D1 overexpression was found in 28 of the 111 cases (25%) and correlated with distant organ metastasis after curative surgery (P = 0.05). The survival rate of patients with cyclin D1 overexpression was significantly lower than that of patients without cyclin D1 overexpression (P = 0.01). A positive correlation between the loss of p16 expression and cyclin D1 overexpression was observed (P = 0. 03). The loss of p16 expression and overexpression of cyclin D1 may be useful prognostic indicators in patients with squamous cell carcinomas of the esophagus. It may be possible to select more suitable treatment for patients with squamous cell carcinomas of the esophagus by evaluating the status of p16 and cyclin D1 expression.

Total cavopulmonary connection without the use of prosthetic material: technical considerations and hemodynamic consequences.

Total cavopulmonary connection with use of an autogenous intraatrial tunnel to create a straight tube between the inferior vena cava and the pulmonary artery was attempted in several types of cardiac anomaly in eight consecutive candidates for the Fontan operation. A small right atrium with an extraordinary location of the inferior vena cava and a short superior vena cava prevented the use of this procedure in two cases. By preserving the crista terminalis and the sinus node and its arteries we prevented the development of postoperative atrial arrhythmias in the short follow-up period, and the P trigger-signal averaged P waves were not different from those of other cardiac anomalies. The proximal stump of the superior vena cava was not incised in any case to enlarge the anastomosis, even when size mismatch between the superior and inferior venae cavae existed, as in a case of bilateral superior venae cavae. Stretching the vessels by approximately 150% was possible and permitted an adequate anastomosis. Cavopulmonary connections via the intraatrial tunnel ensured smooth, nonturbulent, somewhat pulsatile flow without a pressure gradient. We concluded that the creation of an autogenous intraatrial tunnel was possible in many cases without serious complications and that this procedure has potential benefit for the pulmonary circulation in the aspect of pulsatility.

Full-thickness dynamic cardiomyoplasty of the left ventricle with free revascularized latissimus dorsi myografts. An experimental feasibility study.

Dynamic cardiomyoplasty, with use of a free latissimus dorsi myograft revascularized by the internal thoracic artery and vein, was performed in eight dogs subjected to electrical preconditioning for 8 to 12 weeks (group I) and in six unconditioned dogs (group II). The procedure was performed after the resection of the anterior wall of the left ventricle. Cardiac output and left ventricular stroke work were augmented by 23.7% +/- 9.4% and 44.1% +/- 15.9% after graft pacing with 50 Hz burst stimulation at a 1:1 synchronization ratio, while left atrial pressure ranged from 8 to 12 mm Hg. Analysis of the left ventricular function curve showed that graft pacing at rates of 1:1, 2:1, and 3:1 augmented global left ventricular function. Hemodynamic benefit by continuous pacing at a 3:1 ratio was seen for 1.97 +/- 1.90 hours (0.5 to 6.1 hours) in group I until complications unrelated to the graft terminated the study, while it lasted for only 0.19 +/- 0.09 hour in group II. During the stimulation, the ratio of the lactate output to the oxygen consumption of the graft in group I, a possible indicator of metabolic shift, was significantly less than in group II, (0.46 +/- 0.58 and 6.34 +/- 1.73; p < 0.01). We conclude that free grafts of transformed latissimus dorsi muscle can augment global left ventricular performance, with a physiologic preload by oxidative metabolism, and provide a viable option in full-thickness dynamic cardiomyoplasty.

Atrioventricular groove patch plasty for anatomically corrected malposition of the great arteries.

OBJECTIVE: In anatomically corrected malposition of the great arteries, dextroposition of the posterior pulmonary artery and levoposition of the anterior aorta are associated with the leftward deviation of the proximal portion of the right coronary artery away from the right atrioventricular groove. This anatomic feature allows a transannular subpulmonary patch plasty of the right ventricular outflow tract along the right atrioventricular groove between the right coronary artery and the tricuspid anterior anulus (ie, atrioventricular groove patch plasty) for relief of subpulmonary stenosis without jeopardizing the right coronary artery. METHODS: This report describes the midterm results of a new surgical technique, atrioventricular groove patch plasty with a monocuspid transannular patch for subpulmonary stenosis, in 3 patients with anatomically corrected malposition of the great arteries, along with a concomitant closure of ventricular septal defects. RESULTS: Postoperative catheterization revealed adequate relief of pulmonary stenosis, with a pressure gradient of 8.0 +/- 3.5 mm Hg and with normalized right ventricular pressure (33 +/- 10 mm Hg), contributing to excellent midterm results with no late death and reoperation during a postoperative follow-up period of 70 +/- 47 months. CONCLUSION: This technique provides a promising alternative to Rastelli-type conduit repair for subpulmonary stenosis in anatomically corrected malposition of the great arteries.

Dynamic aspects of AMPs in the kidney in physiological conditions--their metabolism and turnover.

The past few decades have witnessed a number of studies on AMPs in the kidney. Almost all of these studies, however, have dealt with the quantitative and qualitative analysis of AMPs in the kidney using biochemical techniques, whereas the dynamic aspect of AMPs in the kidney has been overlooked and its metabolism and turnover have never been emphasized. On the other hand, the kidneys removed from humans and experimental animals revealed a wide variety in interstitial tissue in the medulla microscopically and in the papilla of the kidney macroscopically. The reasons for these variations in the medulla, its mechanism and the matrical component have not yet been clarified. In an effort to clarify these points, we herein describe our study on the dynamic aspect of AMPs in kidney histologically in relation to their biological turnover which we employed several staining methods. Our results revealed that there was a very active turnover of AMPs present in the kidney confirming that the kidney plays an important role physiologically in AMP metabolism. The degree of the turnover of AMPs in the kidney varies from case to case. In the active phase, AMPs are excreted in the glomerulus and reabsorbed in the proximal portion of the collecting tubules. Most of the absorbed AMPs are finally drained through the lymphatic vessels in situ and a few are excreted into the urine. Contrary cases have been demonstrated, however, only were a few AMPs were noted throughout the nephrons in the kidney. AMP turnover in the kidney is unexpectedly remarkable. The medulla, which has been considered less important, in fact, plays a key role in AMP metabolism.

[Some techniques for the correction of the congenital heart disease with autologous flap].

14 living flaps in 8 children were used to repair for the congenital heart disease, because artificial material and xeno grafts were shrunk in growing children but living flaps were going to glow with children. It were possible to use the living flaps to reconstruct of pulmonary outflow in truncus arteriosus, for septoplasty in partial anomarous of pulmonary venous return and reconstruction of unloofed coronary sinus in endocardial defect with triatriatum and intraatrial tunnel in TCPC or Fontan type operation.

[Clinicopathological study on primary lung cancer--immunohistochemical expression of p53 suppressor gene and bcl-2 oncogene in relation to prognosis].

Two hundred and eleven surgically resected primary lung tumors were studied immunohistochemically. According to histologic type, they were 129 adenocarcinomas, 56 squamous cell carcinomas, 4 small cell carcinomas, 8 large cell carcinomas, 8 adenosquamous cell carcinomas, 5 so-called carcinosarcomas and 2 other tumors. Immunohistochemical expression of p53 and bcl-2 was studied in relation to the disease-free survival. Among the 211 patients with lung cancer, 109 were positive for p53 expression, and there was no significant relationship between p53 expression and sex, or clinicopathological stage and size of the tumor, although the patients with squamous cell carcinoma had a significantly higher frequency of p53 expression than those with adenocarcinomas. The frequency of p53 expression was significantly higher in the patients with poorly differentiated adenocarcinomas than in those with other histologic types. Seventy four of the 211 patients were positive for bcl-2 expression and bcl-2 expression was higher in the stage I patients and patients with small lung tumors 2cm or less in diameter than in the other patients. The patients with adenocarcinoma had a higher frequency of expression than those with squamous cell carcinoma but no difference was found in the histological differentiation of the tumor. The 5-year survival of patients positive for p53 expression was poorer than that of those with negative expression and the survival rate was higher in the patients positive for bcl-2 expression than in those with negative expression. These findings suggested that the expression of p53 and bcl-2 is a useful marker of follow-up and prognosis, but will require more data concerning the mechanism of carcinogenesis. Seven cases of primary lung cancer were examined for genetic abnormality of the p53 gene. cDNA was synthesized from total RNA of primary tissues of lung cancer using oligo (dT) primer and reverse transcriptase and polymerase chain reaction (RT-PCR), and PCR-single strand conformation polymorphism (SSCP) analysis were performed. Five patients gave a positive result upon PCR-SSCP analysis of the p53 gene. To confirm the results of PCR-SSCP analysis, their nucleotide sequences were further analyzed and four of them had point mutations at different codons (154, 176, 207, 236) and one had deletion of one nucleotide (245) in exon 5 and 8. Fifteen percent of 26 patients with small peripheral lung adenocarcinomas less than 2cm in diameter were already advanced in stage and various factors such as vascular invasion, pleural involvement and degree of scar grade were higher than in patients with clinicopathological stage I. In advanced cases, the frequencies of p53 expression was higher than in stage I cases. Concerning the relationship of the degree of scar grade to PDGF-B expression, we demonstrated the production of PDGF-B protein immunohistochemically and the expression of PDGF-B-mRNA by In situ hybridization in the adenocarcinoma cells and macrophages of the lung tumors. However, no significant correlation was observed between the degree of PDGF-B expression and collagen production in the fibrotic focus.

[New configuration of right ventricular dynamic cardiomyoplasty by latissimus dorsi for hypoplastic right ventricle].

UNLABELLED: The purpose of this experimental study is to evaluate the efficacy of linear-type right ventricular (RV) dynamic cardiomyoplasty in a setting of patch enlargement model for hypoplastic RV. In 6 puppies (6-8 kg), under a cardiopulmonary bypass (CPB), RV free wall and septal traveculation were resected and replaced with large pericardial patch, simulating RV patch enlargement of hypoplastic RV. A pedicled left LD, anchored to 3rd rib, wrapped onto the RV patch in parallel to RV long axis, while LD fixed to only RV diaphragma surface without wrapping LV surface. After the termination of CPB, LD flap was synchronously paced at 1:1 ratio with cardiac beat with a trained-pulse stimuli (10-25 Hz). RV performance was tested by RV function curve (RVSWI vs CVP) and RV pressure-volume relationship (ESPVR) assessed by conductance catheter. RESULTS: LD graft stimuration showed significant augmentation of PAP (145 +/- 21%), PA flow (152 +/- 21%) and AP (128 +/- 23%) at CVP of 10 mmHg. RV function curve and ESPVR confirmed dramatical augmentation of RV performance by graft stimulation, which was identical to preoperative normal RV function even at the low CVP range. CONCLUSIONS: Linear LD myoplasty after patch enlargement of RV may viable surgical option for hypoplastic RV.

[Transportation for a pediatric heart transplant candidate to Germany].

A 8-year-old girl who underwent a total cavopulmonary connection as an one-staged repair for tricuspid atresia (Ic) had had a progressive dilated cardiomyopathy. Despite of any medical support, her left ventricular ejection fraction had been ranged from 10% to 20% since 4 months after Fontan operation. This patient was decided to apply for a heart transplantation in Germany 17 months after Fontan operation. An administration of the sufficient amount of inotropics and oxygen, volume resuscitation, reduction of the peripheral circulation at the time of take-off, and a meticulous monitoring may contribute to the successful transportation of the critically ill patient.

[Midterm results of total aortic root replacement with pulmonary autograft (Ross operation)].

Between February 1995 and December 1999, 18 patients underwent Ross operation. Age at the operation ranged from 2 to 31 years. Diagnosis includes congenital aortic stenosis and/or regurgitation in 15, and adult aortic regurgitation in 3. In all cases autograft was implanted by the method of total aortic root replacement, associated with annuloplasty for the dilated aortic annulus in 2 and aortoventriculotomy by the Konno procedure in 3 (Ross-Konno). Right ventricular outflow tract was reconstructed by a pulmonary homograft in 12, a xenopericardial conduit in 3, or the other reconstructive procedures with autologous tissue and outflow patch in 3. There was no operative and late death. Reoperation was needed in 1 patient due to stenosis of pericardial conduit 4 years after the initial operation. Pressure gradient across implanted autograft valve was negligible (4.8 +/- 0.5 mmHg), and echocardiography revealed no aortic regurgitation in 12 cases and trivial to mild in 6, over a mean follow-up period of 23 +/- 18 months (range 2 to 60 months), signifying excellent durability of implanted autograft. Right ventricular outflow tract reconstruction with the homograft resulted in excellent mid-term performance as showing pressure gradient of 9.0 +/- 4.6 mmHg and no regurgitation in 11 of 12 cases, whereas pressure gradient was 17.9 +/- 13.1 mmHg in the patients underwent the other reconstructive procedures. We conclude that Ross procedure associated with the concomitant procedures to adjust the size discrepancy between the native aortic annulus and autograft has provided good midterm results with excellent autograft durability. And this procedure was thought to be a preferable method for children as well as young adults with congenital aortic stenosis.

[Analysis of 293 cases of hepatocellular carcinoma of recent ten years--I. Epidemiology, anamnesis and tumor occupying rate].

Two hundred and ninety-three cases of hepatocellular carcinoma (HCC) admitted to the key hospital of the rural area of western Japan, Saga Prefectural Hospital, during 10 years since 1979 to 1988 were analysed retrospectively. The male to female ratio was 3.7 to 1 and the ratio of HBs-Ag positive to negative was 3.5 to 1. The peak of the age distribution was seventh decade. The incidence increased annually, especially in HBs-Ag negative males. Their past history of blood transfusion was considered as an etiology of HCC in 19 (9.9%). The HCC was diagnosed approximately 10 years earlier in habitual drinkers than non-habitual drinkers of both positive and negative HBs-Ag. The incidence of small tumors is associated with the past history of chronic liver disease, negativity of HBs-Ag, lack of symptoms and old age.

[Analysis of 293 cases of hepatocellular carcinoma of recent ten years--II. Diagnosis, therapy and prognosis].

Two hundred and ninety-three cases of hepatocellular carcinoma (HCC) of recent ten years during 1979 and 1988 were analysed on its diagnosis, therapy and prognosis. Angiography was the most useful diagnostic method for the first 5 years. During recent 5 years and for the tumor with size less than 2 cm, however, ultrasonography was the best method. 24.7% cases showed negative AFP and only 42.5% cases showed the level over 400 ng/ml. According to the tumor occupying-rate at the diagnosis, the number of cases of E1 had increased annually, the other cases being unchanged. 88.6% cases had liver cirrhosis microscopically as being reported previously. As a therapy TAE was most frequently performed, followed by operation, arterial infusion of antitumor drugs et al. The prognosis of the patients depended on the tumor occupying-rate. For the case of E1, the prognosis was the best by the therapy of ethanol injection therapy, operation and TAE. For the cases with tumor of larger than E1, frequent TAE was the best. From these results we concluded that we must make efforts to find small tumors to get the good prognosis.

[Telomerase assay for diagnosis of esophageal cancer].

Esophageal squamous cell carcinoma is one of the aggressive diseases that has poor outcome. Therefore it is appeared that early diagnosis is very important for improving its outcome. Iodine staining method is useful for detecting the abnormal squamous epithelium and unstaining lesions by iodine contain the early esophageal cancers. Recently, telomerase activity that provides an immortal capacity for the cells has been measured in many tissues. We measured the telomerase activity in the samples of unstaining lesion by iodine using a polymerase chain reaction-based assay and described the relation between telomerase activity and histopathological findings.

[Present status of cardiomyoplasty].

Direct ventricular assist and myocardial replacement using skeletal muscle, so-called dynamic cardiomyoplasty, are promised as an effective treatment of choice in severe cardiac failure. Owing to the use of autologous muscle, the risk of rejection can be ignored, which is problematic in cardiac transplantation. More than 300 cases have been reported in the world. Since a cardiac transplant protocol has not been started yet in our country, we are hoping that clinical experience with these treatments solves our problem.

[Successful direct embolectomy for acute massive pulmonary thromboembolism].

A 35-year-old woman was bedridden because of a fall and developed pulmonary embolism after venous thromboembolism of lower extremity. Although anticoagulation therapy was immediately carried out, hemodynamics deteriorated gradually into the state of class IV in Green-field's classification. As a result, an urgent surgical procedure was performed. Under moderate hypothermic cardio-pulmonary bypass, the aorta was cross-clamped and the pulmonary artery was opened. An 18 gram clot was taken out directly and other small pieces of clot were removed with a fiberscope, a Fogarty catheter and an aspirating tube. After surgery the patient recovered from symptoms efficiently. Some cases of acute pulmonary thromboembolism have been reported, however, the generalized classification and surgical indication for this disease have not been established yet. But, as all of reports mentions, surgical procedure is recommended positively to these cases that resist anticoagulation therapy.

[One and one half ventricle repair for pure pulmonary atresia--a case report].

One and one half ventricle repair consisting of the Glenn operation and the right ventricular outflow tract reconstruction was performed in a 4-year-old boy. The diagnosis of this patient was pure pulmonary atresia. He had undergone Brock's operation, Blalock-Taussig shunt and a central shunt at neonatal period. At the time of one and one half ventricle repair, the connection between the superior vena cava and the right atrium was left open. Although the RVEDV was 34.3% of normal, the topology of the right ventricle was tripartite. At three months after one and one half ventricle repair, RVEDV increased up to 52.7% of normal. This data suggests that a further definitive surgery, i.e., complete biventricular repair could be applicable in the future.

[Report of a case of the anomalous origin of the right coronary artery from the pulmonary artery with atrial fibrillation and bradycardia].

A 62-year-old man who was referred to implantation of pacemaker on account of severe bradycardia revealed anomalous origin of the right coronary artery from the pulmonary artery on aortography. The aortic root cineangiogram demonstrated single left coronary artery arising from the aorta with retrograde filling of the right coronary artery (RCA) which drained into the main pulmonary artery. Chest X-ray revealed marked cardiomegaly and treadmill exercise test shows positive at stage 2 of the Bruce protocol. Operation was performed under cardiopulmonary bypass. Although we tried to transplant the RCA to the aorta, the arterial wall was very fragile and could't bear arterial pressure. Therefore the RCA was ligated at its origin and disconnected from the pulmonary artery. Post operative course was uncomplicated and the patient was discharged without any symptoms.