[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.

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.

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.

Influence of coexisting cirrhosis on long-term prognosis after surgery in patients with hepatocellular carcinoma.

BACKGROUND: As one of the reasons for the poor prognosis of patients with hepatocellular carcinoma (HCC) and cirrhosis, the influence of cirrhosis itself has not been clarified. METHODS: We compared the postoperative long-term courses of patients with HCC and cirrhosis with the courses of patients with HCC and without cirrhosis to determine how the coexisting cirrhosis affected the prognosis after surgery. The patients with HCC who underwent curative hepatic resection consisted of 142 with associated histologically confirmed cirrhosis and 48 without cirrhosis. RESULTS: The 5-, 7-, and 9-year survival rates were 44%, 32%, and 26%, respectively, in the patients with cirrhosis and 68%, 57%, and 57%, respectively, in the patients without cirrhosis. The prognosis of the group with cirrhosis was significantly worse than that of the group without cirrhosis. The main cause of death in both groups was cancer recurrence. The patients with cirrhosis had significantly lower recurrence-free survival rates at 3 years and later than had the patients without cirrhosis. A comparison of the background factors revealed no substantive disadvantages with regard to tumor-related and surgical factors in the patients with cirrhosis compared with the patients without cirrhosis. The recurrence-free survival rates after minor and major resection indicated fewer disadvantages of limited hepatectomy in the group with cirrhosis than in the group without cirrhosis. Moreover, the recurrence-free survival of the group with cirrhosis was shorter at less advanced stages than at more advanced stages when compared with that of the group without cirrhosis. CONCLUSIONS: The higher carcinogenic potential in cirrhosis could be presumed to be the most likely reason for the poorer prognosis after surgery in the patients with HCC and cirrhosis.

The prognostic significance of surgical margin in liver resection of patients with hepatocellular carcinoma.

OBJECTIVE: To evaluate the prognostic significance of surgical margin in liver resection of patients with hepatocellular carcinoma. DESIGN: Retrospective study. SETTING: The Center for Adult Diseases, Osaka, Japan, between 1980 and 1989. PATIENTS: One hundred eighty-five patients with hepatocellular carcinoma who underwent liver resection with complete extirpation. MAIN OUTCOME MEASURE: Cumulative survival rate. RESULTS: The patients were divided into a wide surgical margin group, in which the lesion was excised with a margin of 1.0 cm or more, and a narrow surgical margin group, in which the margin was less than 1.0 cm. No significant differences could be detected in survival rates for 3 years or longer. Mean +/- SE tumor sizes were 3.4 +/- 0.4 cm and 4.4 +/- 0.3 cm, respectively, in the wide and narrow surgical margin groups. The patients were divided into three groups according to tumor size: group 1, 2.0 cm or less in diameter; group 2, greater than 2.0 cm but 5.0 cm or less in diameter; and group 3, greater than 5.0 cm in diameter. In groups 2 and 3, no significant differences in survival rates were found between the wide and narrow surgical margin groups. In group 1, the survival rate was significantly higher in the wide surgical margin group than in the narrow surgical margin group (P < .05). CONCLUSIONS: Small hepatocellular carcinomas of 2.0 cm or less in diameter should be resected with an adequate surgical margin. However, surgical margin was not a significant factor in the resection of hepatocellular carcinomas larger than 2.0 cm.

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.

Necrosis of hepatocellular carcinoma caused by spontaneously arising arterial thrombus.

This paper describes a 65-year-old Japanese man with hepatocellular carcinoma (HCC) in whom the alpha-fetoprotein level decreased remarkably without any treatment. Plain computed tomography disclosed a low-density area in the left lateral segment. Liver scintigraphy revealed a filling defect with 99mTc-Sn colloid and increased uptake of 67Ga-citrate. The latter was smaller in area than the former. This indicates that non-necrotic HCC was still present at this time. There was no hypervascular lesion in the hepatic angiogram obtained 22 days after liver scintigraphy. The tumor was resected by partial hepatectomy 24 days after hepatic angiography. The histological section showed almost complete necrotization of the tumor, and the necrotic change consisted of old and recent necrosis. An arterial thrombus was formed in non-tumor liver tissue. It was presumed that coagulative necrosis was produced by interruption of the blood supply due to the spontaneous formation of an arterial thrombus.

Palliative surgical treatment for recurrent and non-resectable hepatocellular carcinoma.

Of 275 patients who had a radical hepatic resection for HCC, 143 (52%) experienced recurrences. Of these 143 patients, the liver was the site of first recurrence in 130 patients (91%). The first form of therapy for recurrent patients was transarterial chemoembolization (TACE) in 82 (74%), hepatic resection in 15 (14%) and percutaneous ethanol injection in 6 (5%) of the 111 patients who received regional therapy. Post-recurrent survival rates of TACE and hepatic resection were 37%, 77% at 3 years and 17%, 77% at 5 years, respectively. Wrapping therapy was performed in seven patients, two of whom had received repeat TACE for intrahepatic recurrence; the remaining 5 were unresectable cases. After wrapping therapy, the area of previous collateral feeders was be supplied by the hepatic artery. The high level of AFP decreased dramatically. This procedure resulted in a complete response in 2 patients, a partial response in 3 and no change in 2. Overall survival was 4-54 months, and the median survival was 18 months. Two patients are still alive, 18 and 20 months after the procedure.

Apoptosis of acinar cells in the pancreas of rats fed on a copper-depleted diet.

Male Fischer 344 rats weighing 80-90 g were fed on a copper-depleted diet supplemented with 0.6% triethylenetetramine tetrahydrochloride (a copper chelator), and the death of pancreatic acinar cells of these rats was investigated morphologically and biochemically. The weight of the pancreas of these rats decreased from 3 weeks after feeding, and concomitantly the percentage of dead acinar cells increased to the maximum in about the 5th week and decreased subsequently. These dead acinar cells showed light microscopic and electron microscopic characteristics of apoptosis. Furthermore, the electrophoretic pattern of DNAs extracted from the pancreas having many dead acinar cells showed a ladder-like distribution, characteristic of apoptosis. The present results indicate that feeding of rats on a copper-depleted diet supplemented with a copper chelator results in apoptosis of acinar cells of the pancreas.

Margin quality and microleakage of Class II composite resin restorations.

Margin quality and isotope microleakage analyses of Class II restorations placed in extracted human molars were compared using various composite resins and placement techniques. At occlusal margins, the traditional (experimental) composite resin restoration placed by the incremental technique showed less microleakage than did the traditional (commercial) [corrected] composite resin restoration placed by the bulk technique. In each group, the occlusal and proximal adaptations had significantly higher "excellent margin" than did the cervical adaptation. Thus, the marginal adaptation at the cervical aspect of conventional Class II composite resin restorations may present a problem with respect to microleakage.

[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.

[A case of malignant hemangioendothelioma of the lung with rapid growth of pulmonary metastasis].

Malignant hemangioendothelioma of the lung is very rare and difficult to diagnose. The growth is rapid and the prognosis is very unfavorable. We report an operated case of the disease with rapid growth of pulmonary metastasis. The silver, vimentin and factor VIII stainings were available for diagnosis of this disease. The 46-year-old female patient died of bleeding from the pulmonary metastasis eight months after the operation without other distant metastasis. Even if a lung tumor is pointed out and thought to be benign, frequent follow up is necessary. Furthermore, we recommend positive lung biopsy by thoracotomy or video-assisted-thoracic-surgery.

[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.

[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.

[Pharmacokinetics following intraperitoneal sequential administration of cisplatin and fluorouracil for gastric cancer].

Gastric cancer patients with peritoneal dissemination underwent a palliative resection of the stomach and received an intraperitoneal administration of CDDP (70 mg/m2) and 5-FU (700 mg/m2), immediately after the surgery. The levels of CDDP and 5-FU in serum and peritoneal cavity were serially monitored in order to study the pharmacokinetics of these drugs. group A (n = 9): CDDP dissolved in 500 ml saline was infused intraperitoneally at 200 ml/min, and one hour later, 5-FU dissolved in 500 ml saline was infused at the same speed. The infusion catheter was clamped for two hours after completion of 5-FU infusion. Group B (n = 3): CDDP in 500 ml saline were infused at 10 ml/min and then 5-FU in 500 ml were infused at 5 ml/min. Group C (n = 2): CDDP in 1,000 ml saline was infused at 200 ml/min. Group D (n = 2): 5-FU in 1,000 ml saline was infused at 200 ml/min. The free CDDP levels in the peritoneal cavity were 22 micrograms/ml in group A, 57 micrograms/ml in group B, and 13 micrograms/ml in group C at one hour after completion of the infusion. The 5-FU levels in the peritoneal cavity measured two hours after completion of the infusion were significantly higher in the group B (349 micrograms/ml) than in group A (132 micrograms/ml) and C (71 micrograms/ml). The Cmax of 5-FU in serum was lowest in group B. The AUCs in the peritoneal cavity of free CDDP and 5-FU were 63.6 micrograms.hr/ml and 925 micrograms.hr/ml, respectively. These values were above the 10th percentile of IC90 for gastric cancer. No serious complications were encountered in group A and B where both CDDP and 5-FU were administered as compared with group C and D, where either CDDP or 5-FU was administered.

[Evaluation of intra-arterial infusion chemotherapy and radical pancreatectomy in patients with locally advanced pancreatic cancer].

This is a retrospective study to evaluate arterial infusion chemotherapy and resection for locally advanced pancreatic cancer involving retro-peritoneal organs or large vessels such as superior mesenteric artery or celiac trunks. Intra-arterial chemotherapy was performed for 19 patients, and 15 underwent pancreatectomy. Patients in the intra-arterial chemotherapy group could live 11 months out of the hospital, against 4 months in the resected cases (p < 0.05). The period of over 2nd degree in performance status was 11 months in the arterial chemotherapy group and 3 months in resected groups (p < 0.05). The survival rates were 53, 18 and 9% at 1, 2 and 3 years in the patients with arterial chemotherapy, respectively, against 22, 15 and 15% in the resected patients (p < 0.05). These results suggested that intra-arterial chemotherapy was significantly effective in prolonging the survival period with a better quality of life.

[Significance of preoperative TAE as an adjuvant therapy for hepatocellular carcinoma].

In 304 patients with hepatocellular carcinoma who underwent hepatic resection, 162 patients received chemoembolization before surgery (group A) and the remaining 142 patients received no therapy before surgery (group B). The 5-year disease-free survival (DFS) of group A and B were 36% and 21%, respectively, and there were no significant differences between them. In the groups of patients with good liver function (Child A), or patients with solitary tumor, or patients with tumors more than 5 cm in size, DFSs of group A were significantly better than those of group B. The difference of DFS between group A and B was largest in the group of the patients with tumors more than 5 cm in size.

["Partial wrapping therapy" for recurrent hepatocellular carcinoma by transthoracic route].

Two patients with recurrent hepatocellular carcinoma close to the diaphragma, underwent TAE following decollateralization using silicone rubber sheeting with thoracotomy. The patients suffered from severe liver cirrhosis. Laparotomy was not carried out for the preservation of hepatic function. After wrapping therapy, serum AFP level was reduced to almost the normal range in one case, but in another case to half because of bilateral lung metastasis. The maximum serum level of postoperative serum total bilirubin in these 2 cases was 2.0 mg/dl and 1.6 mg/dl, respectively. We think wrapping therapy with thoracotomy is readily applicable for patients with severe cirrhosis.