Haruo Ohkawa

Experimental analysis of the Ill effect of anomalous pancreaticobiliary ductual union

An ideal canine model of anomalous pancreaticobiliary ductal union, similar to a human anomaly, was devised. Direct anastomosis of the dorsal pancreatic duct and the choledochus was employed (dorsal pancreaticocholedochostomy). The ventral pancreatic duct was not manipulated. Cylindrical choledochal dilatation results in 13 out of 20 adult dogs and in 4 out of 6 puppies. Dilatation of the intrahepatic biliary tree and thickening of the choledochal wall in a hepatic direction were observed in high ratio among adult dogs. Puppies had less dilatation. The activation of pancreatic enzymes was studied in bile containing pancreatic juice. The proteolytic enzymes, trypsin and elastase were proven to be activated in the bile without the presence of enterokinase in the pancreaticocholedochostomy model. This would be the cause of the ill effects of refluxed pancreatic juice into bile in anomalous pancreaticobiliary ductal union.

Complete Resection Is Not Required in Patients With Neuroblastoma Under 1 Year of Age

BACKGROUND/PURPOSE The prognosis of neuroblastoma (NB) patients when detected before 1 year of age is excellent, particularly in patients whose disease is detected by screening. In some institutions patients with stage I or II NB detected by screening have been observed closely without any treatment. Most showed tumor regression or maturation and are surviving without tumor resection. Resection of infantile NB sometimes is complicated by vascular accidents resulting in vanishing kidney or intestinal infarction. The role of surgery in the treatment of infantile NB therefore is becoming controversial. The authors have treated infants who have easily resectable primary tumors with resection and sampling for lymph node metastases. If the resection of the primary tumor seemed difficult, only biopsy was performed initially followed by chemotherapy with or without resection. The authors analyzed the clinical outcome of the infantile NB in their institution to elucidate the role of surgery in this particular group of patients. METHODS Thirty-six patients less than 12 months of age were treated between 1982 and 1997. Twenty-five patients who showed no symptoms had NB detected by screening at 6 months. Five patients had stage IVS disease in early infancy. No patients had bone or remote lymph node metastases. N-mycamplification was not detected in any of the 28 tumors examined. There were four diploid and 12 near-triploid tumors. RESULTS Complete resection was possible in 13 stage I and II patients without any complications. Obvious lymph node metastases were not resected in 13 patients with stage II or III NB. Partial resection leaving gross residual disease was accomplished in three patients with stage III NB. Surgical resection was not attempted in four patients because of unresectability in three patients with stage III or IVS disease and because of marked tumor shrinkage after a short course of chemotherapy in one patient with stage III NB involving the celiac axis. A neonatal cervicomediastinal stage III NB recurred very rapidly after partial resection but started to regress spontaneously 2 months postoperatively. Another neonatal stage II cervical NB progressed to stage IVS with hepatomegaly causing respiratory distress but regressed spontaneously. All the patients are alive and disease free without surgical morbidity. CONCLUSION All of the 21 patients who underwent partial tumor resection with or without chemotherapy are alive and doing well without tumor, indicating that complete resection is not required in this particular group of patients.

A murine model for bone marrow metastasis established by an i.v. injection of C-1300 neuroblastoma in A/J mice

A reproducible tumor model for bone marrow metastasis has been developed by an injection of murine C-1300 neuroblastoma (C-1300 NB) cells into the tail vein of syngeneic A/J mice. The animals died with liver metastases at 18–21 days after an injection of 105 tumor cells and often had bone marrow metastasis in the femur. N-methylformamide (NMF), a maturational agent, was administered to inhibit liver metastases and to extend survival in mice with advancing bone metastasis. Histological examination of bone marrow metastasis, demonstrated lesions varying from a few small colonies of C-1300 NB cells either in metaphysis or diaphysis to large foci replacing normal hematopoietic bone marrow, simultaneously invading epiphysis or cortex of bone as bone metastasis. This assay demonstrated the ability to detect neuroblastoma cells in the bone marrow histologically and could determine bone marrow TD50 by extraction of bone marrow cells after treatment with various doses of drug. Fifty per cent of mice injected with cyclophosphamide (CY) developed bone marrow metastasis without liver metastasis. Treatment with tamoxifen, an anti-calmodulin drug, suppressed tumor takes in the recipient mice with tamoxifen-dose-dependent fashion. This experimental system allows for investigations into the therapeutic response and biology of neuroblastoma metastases in the bone marrow.

Three-dimensional analysis of anorectal embryology

To clarify the embryological etiology of various malformations, we recently developed a computerized three-dimensional (3D) reconstruction system for analytical observation of real structures in a small fetus and applied this technique for the analysis of anorectal embryology. Fifty-one pig fetuses were obtained from two porcine families with anorectal malformations established in our facilities. They were sectioned sagitally and 3D structures of the anorectum were reconstructed from serial sections and analyzed. In the young pig embryo (24–30 days), the cloaca exists as a cloacal plate, a very thin, flat structure vertical to the body surface. It is filled with basophilic cells and contains no cavity. Therefore, the body surface covering the urogenital and rectal area may not be recognized as a single membranous structure. In the reconstructed image of the cloacal plate, the proximal part, which lies between the hindgut and tail groove, was defective in the specimens with anorectal anomalies whereas the cloacal plate existed from the entire anterior part to the posterior ene of the tail groove in the normal specimens. This result supports the theory of van der Putte that anorectal malformations are caused by a defect of the cloacal plate between the hindgut and tail groove.

Age-related changes in hepatic drug-oxidizing activity using trimethadione as a probe drug in human

Objective: The purpose of this study was to examine the changes in trimethadione (TMO) metabolism over seven stages from neonates to elderly adults. Methods: The subjects were divided into seven groups according to age: neonates (<4 weeks; n=5), infants (<12 months; n=12), children (<10 years; n=21), adolescents (<20 years; n=3), young adults (<40 years; n=20), mature adults (<65 years; n=20) and elderly adults (⩾65 years; n=40). The metabolism of TMO following oral administration (4 mg/kg) was studied in 21 healthy volunteers and 100 patients. Results: The serum albumin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were always within normal ranges. The serum dimethadione (DMO) versus TMO ratio (DMO/TMO) at 4 h after administration of TMO was low in neonates (mean±S.E.M.: 0.12±0.01). In infants, however, it reached approximately 95% of the peak observed in adolescents (0.64±0.09), and gradually decreased thereafter. Conclusion: These findings indicate that the metabolic rate of TMO varies according to the stage in life. Using TMO as a probe drug may be of value in determining changes in overall hepatic drug-oxidizing activity throughout the human life-span, thereby allowing evaluation of drug–drug interactions and clinically significant risks associated with drug therapy.

Extensive epidural teratoma in early infancy treated by multi-stage surgery.

Abstract We report a rare case of extensive extradural teratoma successfully treated by multi-stage laminotomy and thoracotomy. A 34-day-old, dyspneic infant had a large posterior mediastinal mass identified on a chest X-ray radiograph. Imaging studies disclosed that the mass originated from the extradural space at the level of the lower thoracic spine, extending cephalad to C4 and caudad to L4 and severely compressing the spinal cord anteriorly, causing paraplegia. The tumor expanded bilaterally through the intraspinal foramina, coalescing to form a huge mediastinal mass. The upper half of the teratoma was removed utilizing a laminotomy from T3 through T9; 2 months later the lower half was excised via a laminotomy from T11 to L3. An additional procedure was required to resect recurrent tumor through a laminotomy from T8 to T12. The reconstructed vertebral arches were well-preserved in shape, with an almost normal spinal canal.

Endoscopic septotomy: A new surgical approach to infantile hydrometrocolpos with imperforate hemivagina and ipsilateral renal agenesis

The authors propose a new surgical approach for neonates and infants with hydrometrocolpos caused by double vagina and imperforate hemivagina. Usually for these patients, laparotomy is a common approach used to decompress the obstructed hemivagina. The authors compared the characteristics of three options used to relieve obstruction of the hemivagina using endoscopic, transvaginal, and laparotomy approaches. An endoscopic septotomy (colposcopic approach) using the Storz neonatal resectoscope is less invasive and less expensive than other methods. We emphasize that endoscopic septotomy is a feasible surgical method to relieve the obstructive symptoms related to imperforate hemivagina.

Cholangio-venous reflux as a cause of recurrent hyperamylasemia in choledochal dilatation with anomalous pancreaticobiliary ductal union: an experimental study.

Cylindrical choledochal dilatation, associated with anomalous pancreaticobiliary ductal union, causes recurrent episodes of right hypochondrial pain, vomiting, and fever. The symptoms are very often accompanied by hyperamylasemia, which is generally considered to be due to acute pancreatitis. However, our clinical experience and experimental studies have led us to the conclusion that pancreatitis is not the sole cause of hyperamylasemia. In this paper we report our further investigations of the cause of the hyperamylasemia. In 22 mongrel adult dogs, intracholedochal infusion was performed under a continuous hydrostatic pressure of 20 cm H2O for 2 hours. Solutions of amylase from three different sources and a lipase were used in the range of concentrations found clinically in the bile within a cylindrical choledochal dilatation. In the 3 groups, hyperamylasemia was proven by quantitative estimation of serum amylase level and/or by the changes in specific amylase isozymes. Lipase was also shown to transfer into the blood stream. In an additional experiment on 5 dogs, only the extrahepatic biliary tree, including the gallbladder, was infused with a solution of amylase from Bacillus subtilis. This produced no increase in the serum amylase. Our experiments suggest that amylase passes from the hepatocholedochal system into the blood stream. This phenomenon has long been known as cholangiovenous reflux.

Clinical experience with a sucking sump catheter in the treatment of esophageal atresia

This is an introduction to the sucking sump catheter as a method of continuous salivary suction from the oral cavity for the treatment of esophageal atresia and other diseases. Upper pouch suction on many occasions is not easy. The double lumen catheter was devised by Replogle to achieve better suction efficiency, but this is not always satisfactory. Therefore, we devised an oral suction catheter that is a sucking sump catheter. A no. 8 French Argyle Salem sump catheter was transformed; we added five to six holes, and the tip was bent into a double or triple circle. This is sucked on, as a nipple would be, by the infant. From 6 years of experience, we have determined that this works very well for continuous salivary aspiration from the oral cavity, that it causes no complications; this device can also contribute to early oral feeding after esophageal anastomosis.

The clinical importance of the trimethadione tolerance test as a method for quantitative assessment of hepatic functional reserve in patients with biliary atresia

Background: The trimethadione (TMO) tolerance test was performed to evaluate its usefulness in the assessment of hepatic functional reserve in patients with biliary atresia.