Increased mucosal ornithine decarboxylase activity in human gastric cancer.

The induction of ornithine decarboxylase (ODC), a key enzyme of polyamine biosynthesis, is an early and obligatory event in the tumor-promoting step in animal models. The enzyme activity is also elevated in some human premalignant lesions. We determined the ODC activity in human gastric cancer tissue and in the mucosa of cancer-bearing stomach. We concluded that gastric cancer tissue had significantly elevated ODC levels over those of mucosa (157.8 versus 45.7, respectively; P less than 0.05). Among mucosa of the stomach, that of the pyloric gland had higher ODC activity than that of the fundic gland (42.8 versus 21.6, respectively; P less than 0.05). Moreover, mucosa from the cancer-bearing stomach had high ODC activity compared with gastric mucosa without cancer. ODC activity in cancer tissue and mucosa from cancer-bearing stomach was activated by GTP. In rat experiments, the properties of ODC induced by gastric carcinogen were analyzed. Transiently induced ODC by a single gastric intubation of N-methyl-N'-nitro-N-nitrosoguanidine was not activated by GTP whereas constitutively expressed ODC of N-methyl-N'-nitro-N-nitrosoguanidine-induced cancer-bearing stomach was activated by GTP. These results suggest that some tumor-promoting stimuli may be concerned in human gastric carcinogenesis and that mucosal ODC activity may be a useful marker for assessing the risk of gastric malignancy.

The effects on cellular functions of bile acid and trypsin in stagnant bile juice in anomalous arrangement of the pancreaticobiliary duct.

To examine the reasons for the high frequency of biliary tract carcinogenesis in individuals with anomalous arrangement of the pancreaticobiliary duct (AAPBD), we investigated the effects on cellular functions of bile acid and trypsin, which are possible risk factors for carcinogenesis found in stagnant bile juice, using a chick embryo fibroblast culture system. Bile acid was found to increase PGE2 synthesis which has been shown to be increased in premalignant lesions, but to suppress the incorporation of [3H]-labelled TdR into DNA. On the other hand, trypsin increased the incorporation of [3H]TdR into DNA, but did not increase PGE2 synthesis. These results suggest that both the bile acid and trypsin present in the stagnant bile juice in AAPBD act to stimulate cell proliferation, but that their mechanisms of action on cell growth differ. Therefore, the combination of these effects of different types of tumor promoters in the stagnant bile juice in AAPBD may account for the high incidence of carcinogenesis.

Spontaneous carotid cavernous fistula presenting only with cranial nerve palsies.

PURPOSE: To discuss the differences in angiographic findings between cases of spontaneous carotid cavernous fistula with and without the classical triad of symptoms (pulsating exophthalmos, bruit, and conjunctival chemosis). METHODS: With CT, MR, and angiography, we examined 12 cases of spontaneous carotid cavernous fistula, five of whom presented only with cranial nerve palsies. RESULTS: In the seven cases with the triad, the main venous drainage from the cavernous sinus was the superior ophthalmic vein. Only one or two veins drained the cavernous sinus, and cortical venous drainage was not present in any case. In contrast, all but one case with only cranial nerve palsies had at least three venous drainage routes from the cavernous sinus, including cortical venous drainage. CONCLUSION: For the diagnoses of spontaneous carotid cavernous fistula, it is important to know that some patients do not show the classical triad of symptoms. In such patients, early diagnosis and treatment are particularly important because cortical venous drainage and a consequent risk of hemorrhage are frequently present.

An unruptured arteriovenous malformation with edema.

We report a case of unruptured arteriovenous malformation in which an extensive zone of increased signal intensity in the brain parenchyma adjacent to the nidus is demonstrated on T2-weighted MR. This area of perilesional hyperintense signal exerts a compressive effect, suggesting that it represents perilesional edema.

Hemorrhagic venous infarction after excision of an arteriovenous malformation: case report.

A case of arteriovenous malformation (AVM) in which postoperative hemorrhagic infarction developed, probably because of occlusion of the former draining veins, is reported. The hemorrhage developed in the temporal lobe 3 days after the initial operation and was located in the immediate vicinity of the site of the AVM. The following findings suggest that the postsurgical hemorrhage probably resulted from a venous thrombosis: 1) no evidence of residual AVM; 2) delayed onset of the hemorrhage, inconsistent with the time course of a hemorrhage developing according to the breakthrough theory or with insufficient hemostasis with a high-pressure afterload; 3) good correlation between the location of the hemorrhage and the occlusion of the draining veins; and 4) multifocal hemorrhage affecting both the gray matter and the subcortical white matter. Postoperative hemorrhagic infarction caused by thrombosis in the draining veins is rare, but it should be considered as a distinct postoperative complication after removal of an AVM.

Intracellular target for alpha-terthienyl photosensitization: involvement of lysosomal membrane damage.

Intracellular targets for the photosensitizer alpha-terthienyl (alpha T) were examined by fluorescence microscopy and microfluorospectrometry using human nonkeratinized buccal cells. Intracellular distribution of alpha T was observed as fluorescent patches widely dispersed in the cytoplasm. The distribution of the fluorescent patches was compared with that of acid phosphatase activity visualized as an azo dye produced by the fast garnet 2-methyl-4-[(2-methyl-phenyl)azo]benzenediasonium sulfate reaction. Because both the distribution sites coincided, lysosomes were the likely sites of intracellular affinity of alpha T. However, because acid phosphatase is not a specific lysosomal marker, we tried to detect another lysosomal enzyme, beta-galactosidase, to confirm if the fluorescent patches were lysosomes, using fluorescein-di-(beta-D-galactopyranoside) (FDG) as a fluorogenic substrate. Without UV-A (320-400 nm) irradiation of the cells after uptake of alpha T and FDG, no significant fluorescence was observed. In contrast, with prior UV-A irradiation in the presence of alpha T and FDG, the bright yellow fluorescence of fluorescein, which is the digested product of FDG, was clearly detected in the cells by fluorescence microscopy. This observation implied that inflow of external FDG into the lysosomes is caused by lysosomal membrane damage on alpha T photosensitization. The present results indicated that lysosomes are the primary photosensitization site of alpha T.

The effects of a carotid-jugular fistula on cerebral blood flow in the cat: an experimental study in the chronic period.

The purpose of the present study was to investigate the effects of feline carotid-jugular fistula (Spetzler's model) on cerebral blood flow at 8 weeks after creation of the fistula. Using laser-Doppler flowmetry, cortical cerebral blood flow (CBF) on the fistula side was measured in 10 cats, Occlusion of the fistula showed no cortical CBF changes in 6 animals, but transient increases in 4. CO2 reactivity in the closed fistula was preserved. No neurological or histological abnormalities were recognized. These findings suggested that cerebral hemodynamic changes due to Spetzler's CJ fistula model are minimal even in the chronic period after fistulization. Therefore, creation of another experimental arterio-venous fistula model is mandatory for the investigation of hemodynamic changes following resection of a cerebral arteriovenous malformation.

Correlation between intravascular pressure and risk of hemorrhage due to arteriovenous malformations.

The correlation between intraoperative pressure levels measured in the feeding arteries and in the draining veins, and the risk of hemorrhage from arteriovenous malformations (AVMs) is discussed. Feeding artery pressure (FAP) was significantly higher in AVMs with hemorrhage (57 +/- 11 mmHg) than in AVMs without hemorrhage (38 +/- 4), and draining vein pressure (DVP) in the former (24 +/- 5) was significantly higher than that in the latter (13 +/- 5). FAP and DVP were inversely related to the number of draining veins and size of the AVMs. The present study suggests that a high FAP and a high DVP may contribute to the development of hemorrhage from AVMs, and supports previous reports that small AVMs and AVMs with only one draining vein are susceptible to hemorrhage.

The effects of a carotid-jugular fistula on cerebral blood flow in the cat: an experimental study in the acute period.

The purpose of the present study is to investigate the effects of feline carotid-jugular (CJ) fistula (Spetzler's model) on cerebral blood flow (CBF) in the acute period after creation of the fistula. Using laser-Doppler flowmetry, cortical CBF was measured on the fistula side of 11 cats. Temporary occlusion and opening of the fistula led to an immediate increase and decrease, respectively, in cortical CBF. However, CBF returned to baseline within 1 minute, on average. CO2 reactivity in the closed fistula was preserved. It is suggested that cerebral hemodynamic changes due to Spetzler's CJ fistula model are minimal in the acute period after fistulization.

Transabdominal closure of tracheoesophageal fistula: a new procedure for the management of poor-risk esophageal atresia with tracheoesophageal fistula.

Nissen fundoplication results in closure of the tracheoesophageal fistula (TEF) without the necessity for a thoracic operation by preventing both the reflux of gastric contents into the lungs through the distal TEF, and leakage of air into the stomach of less than 30 cm H2O intrapulmonary pressure. This procedure can safely be used even for a poor-risk patient and adequate nutritional support (full-strength milk) can be provided immediately after the fundoplication by a gastrostomy tube because the gastric contents cannot reflux into the lungs. This procedure was performed on two patients with esophageal atresia and distal TEF in Waterston Group C and gave successful results.

Cellular activity in the gallbladder of children with anomalous arrangement of the pancreaticobiliary duct.

BACKGROUND/PURPOSE: Anomalous arrangement of the pancreaticobiliary duct (AAPBD) is closely related to congenital biliary dilatation and frequently associated with biliary tract malignancy. To examine the mechanism of biliary tract carcinogenesis in patients with AAPBD, we investigated histologically the early changes in cell proliferative kinetics of the gallbladder mucosa of children with AAPBD. METHODS: Twenty-three specimens of gallbladder were obtained from 23 children with AAPBD, and six control specimens were obtained from pediatric patients. All specimens were fixed routinely and paraffin embedded and examined histologically with H&E staining and immunohistochemically with monoclonal antibody Ki-67(MIB-1), which reacts with a human nuclear antigen associated with cell proliferation. Ki-67 labeling index (Ki-67 LI) was obtained by counting the numbers of Ki-67-positive cells per 1,000 gallbladder epithelial cells. RESULTS: Significant differences in Ki-67 LI were noted between children with and without AAPBD. Furthermore, Ki-67 LI and the incidence of epithelial hyperplasia of gallbladder were significantly higher in children with AAPBD in whom the major pancreatic duct joined the common bile duct (P-C type) than in those in whom the common bile duct joined the major pancreatic duct (C-P type). CONCLUSIONS: Cellular proliferative activity was increased in children with AAPBD, especially those with the P-C-type anomaly. These results suggest that the early mucosal changes of the gallbladder occurred in early childhood of patients with AAPBD and might be associated with gallbladder cancer. Early diagnosis and early surgical division of the biliary tract and pancreatic duct is recommended for children with AAPBD.

An evaluation of surgical treatment and chemotherapy of advanced neuroblastoma (stage III & IV) with special reference to proliferation kinetics of residual tumors.

Twenty two children with advanced retroperitoneal neuroblastoma and one child with advanced posterior mediastinal neuroblastoma admitted to our clinic were treated as follows. Seven patients (group A) underwent primary resection of tumor immediately after diagnosis. In two patients of this group, the levels of VMA and HVA in urine after surgery decreased to nearly normal (group A-I), while they did not change appreciably in the other 5 patients (group A-II). Seven patients (group B) underwent resection of tumor following complete or partial response to preoperative chemotherapy. Nine patients (group C) did not undergo resection of the tumor except for exploratory laparotomy. Two group A-I patients have survived, free of disease, for 6 months and 12 months after diagnosis. All patients of group A-II died within a year. Residual tumors of 4 patients of this group began to grow explosively just after surgery, although they received persistent postoperative chemotherapy. Four patients of group B survived for more than two years and the two patients of this group who received continuous intra-arterial PGE1 therapy had no postoperative explosive growth of residual tumors. Two patients in group C survived for 20 months and the others died within a year. Primary tumors and metastatic foci responded well to therapy as compared with group A-II, which suggests that presence of primary tumors may inhibit rapid growth of metastatic foci. Resection of primary tumors, therefore, was not always conducive to survival unless residual tumor responded to postoperative chemotherapy.

Renal artery spasm: a cause of acute renal failure following abdominal surgery for neuroblastoma.

Interruption of arterial blood supply to the kidney results in acute renal failure (ARF). We describe a case of ARF caused by renal artery spasm following resection of a large abdominal neuroblastoma, combined with paraaortic lymph node dissection and ipsilateral nephrectomy. The blood flow was reestablished by administration of local anesthetics (lidocaine) into the obliterated renal artery through the angiographic catheter. An urgent angiography was of value for the early diagnosis and treatment of this lesion.

Intraarterial injection of anti-tumor drugs dispersed in lipid contrast medium: a choice for initially unresectable hepatoblastoma in infants.

Intraarterial injection of anti-tumor drugs (THP-ADR, CDDP, 5-FU) dispersed in lipid contrast medium (Lipiodol, Laboratorie Guerbert, France) was used in an infant with initially unresectable hepatoblastoma. Lipiodol complex selectively accumulated in the tumor tissue and may keep the chemotherapeutic agents in the tumor tissue for a longer period of time, and a significant reduction of the tumor with a four-day half-life of alpha-fetoprotein (AFP) was followed immediately after the institution of chemotherapy. Successful resection of decreased tumor by extended right hepatectomy under more favorable conditions was performed 2 months after diagnosis. Intraarterial chemotherapy with Lipiodol was particularly useful in potentiating the cytoreduction of anti-tumor drugs and was also useful in reducing the toxicities of anti-tumor drugs to the host.

Arteriovenous malformation of the jejunum in a child.

Arteriovenous malformation of the intestine is an uncommon cause of gastrointestinal hemorrhage, and the diagnosis can be made only by selective mesenteric arteriography to demonstrate the characteristic appearance. This is a case report of a 16-year-old boy with arteriovenous malformation of the jejunum causing massive rectal bleeding. We advocate the use of selective visceral angiography for diagnosing arteriovenous malformations of the intestine, even in children.

Experimental study on the growth and proliferation kinetics of residual tumor after surgery in mouse neuroblastoma.

In order to elucidate the proliferation kinetics of residual tumors after surgery, experimental studies were performed, using C-1300NB and A/J mice, tumor-host system. Mice were inoculated with C-1300NB cells in the chest and leg simultaneously, and then divided into three groups. Growth curves of chest tumors (residual tumors) in Group B after amputation of the tumor-bearing leg were significantly steeper than those of both Group A, whose tumor-bearing legs were not amputated, and Group C, whose normal legs were amputated, at the same tumor age. 3H-TdR labeling indices of chest tumors of Group B were significantly higher than those of Group A (P less than 0.05). DNA histograms of the chest tumors of Group A uniformly showed a unimodal distribution with a peak in the 2c range. On the other hand, in Group B the peak of nuclear DNA distribution shifted from the 2c range to the 4c range after amputation of tumor-bearing leg. The results indicated that an increase in cells in the DNA synthetic phase occurred in the remaining neuroblastoma after reducing the volume of tumor in host by amputation of tumor-bearing legs.

Congenital cervical neuroblastoma associated with Horner syndrome.

A rare case of congenital neuroblastoma of the neck associated with complete Horner syndrome and respiratory distress is described. The case was successfully treated by total excision secondary to chemotherapy. Horner syndrome was of value for early diagnosis of this lesion.

Voluntary anal continence after surgery for anorectal malformations.

Electromyography (EMG) and measurement of voluntary contraction pressure of the external sphincter muscle were performed in 28 patients, aged 5 to 14 years, to assess the function of the external sphincter after surgical correction of anorectal malformations. Ten normal children, aged 5 to 15 years, served as controls. External sphincter function in patients with high-type anomalies was disturbed in the areas of tonic activity, inflation reflex, and activity during further rectal filling. In patients with low-type or intermediate-type anomalies, function was preserved and was equal to that in normal controls. Phasic activity was observed in patients with all types of anomalies and in normal subjects. Among those with high-type anomalies, the three patients with Kelly's score of less than 2 had voluntary contractions of 20 cmH2O or less. However, the mean voluntary contraction pressures were not significantly different among the three types of anomalies. Therefore, patients with high-type anomalies may acquire compensatory voluntary continence through bowel training.

Biliary manometry in choledochal cyst with abnormal choledochopancreatico ductal junction.

Intraoperative manometry of the biliary tract and measurement of amylase levels in choledochal cysts were performed in seven patients, aged 14 months to 5 years, with choledochal cysts, in an investigation of the pathophysiology of the biliary tract. An abnormal choledochopancreatico ductal junction was observed in these seven patients by preoperative endoscopic retrograde cholangiopancreaticography (ERCP) or intraoperative cholangiograms. All six patients examined showed a high amylase level in the choledochal cyst (5,450 to 46,500 Somogyi Units). The intraoperative manometry of the biliary tract showed that a remarkable high pressure zone as was found in the area of sphincter of Oddi was not found in the area of abnormal choledochopancreatico ductal junction. The pressure recordings also demonstrated that the sphincter of Oddi pressure in the patient with choledochal cyst was increased by gastrin stimulation. On the contrary, no pressure reaction to gastrin or secretin was found in the area of abnormal choledochopancreatic ductal junction. From these results it seems that free reflux of pancreatic juice into the biliary system occurs, and the reflux stream depends upon the pressure gradient between pancreatic ductal pressure and common bile duct pressure because of the lack of a sphincter function at the choledochopancreatico ductal junction.

Biliary tract complications in patients with hypoganglionosis and chronic idiopathic intestinal pseudoobstruction syndrome.

The biliary tract system was studied in two patients with hypoganglionosis and chronic idiopathic intestinal pseudoobstruction syndrome (CIIPS) to evaluate manifestations of these diseases, especially as for underlying motility disorder. In a 3-year-old boy with hypoganglionosis, cholelithiasis was diagnosed and the gallbladder specimen showed a markedly hypoplastic neural plexus on histopathology as was found in his total alimentary tract. In a 2-year-old girl with CIIPS, echo-guided gallbladder wall motility testing demonstrated an impaired response to a ceruletide diethylamine stimulation. These clinical experiences in two patients suggest that these pathological entities may be frequently associated with biliary tract complications not only due to a consequence of total parenteral nutrition, but also due to a possible intrinsic involvement of biliary tract dysmotility.