Tomoaki Urakawa

Study of 16,16-Dimethyl Prostaglandin E2 for Prevention of Stress Ulcer after Hepatectomy of Experimental Cirrhotic Liver and Its Influence on Hepatic Regeneration

The influence of 16,16-dimethyl prostaglandin E2 (16,16-dm PGE2; an agent used for the prevention of stress ulcer after hepatectomy of the cirrhotic liver) on liver regeneration after hepatectomy was studied in rats. The following results were obtained. Ulceration after the stress of 6 h of water immersion was markedly suppressed in rats treated with 30 r/kg of 16,16-dmPGE2 as compared with the untreated controls. In animals that received hepatectomy alone, the gastric pH and gastric mucosal blood flow showed significant reduction from the preoperative levels. In animals that received hepatectomy plus 16,16-dmPGE2 treatment the postoperative reduction in the gastric pH and gastric mucosal blood flow was suppressed, suggesting the effectiveness of 16,16-dmPGE2 treatment in the prevention of stress ulcer after hepatectomy of the cirrhotic liver. The 3H-thymidine uptake percentage and thymidine activity 24 h after hepatectomy and the DNA content 30 h after hepatectomy were significantly higher in animals treated with 16,16-dmPGE2 than in the untreated controls. In animals that were treated intraperitoneally with 50 mg/kg of indomethacin 6 h before hepatectomy the mitotic index 30 h after hepatectomy was markedly lower than that in untreated controls. This indomethacin-induced reduction in the mitotic index tended to be normalized by treatment with 16,16-dmPGE2. These results suggest that 16,16-dmPGE2 treatment effectively prevents stress ulcer and favorably affects hepatic regeneration after hepatectomy of the cirrhotic liver.

Laparoscopic lower anterior resection is equivalent to laparotomy for lower rectal cancer at the distal line of resection

BACKGROUND Procedures that involve resection of the distal rectum challenge the current limitations of laparoscopic technology, because of lack of compact articulating stapling instruments. METHOD We improve the procedure with the aid of a Lap disk, an abdominal wall sealing device that was developed for hand-assisted manipulation. A linear stapler capable of changing its stop angle is inserted through the disk, and the rectum is transected by the disk during a second pneumoperitoneum. RESULTS The transection line becomes equivalent to that obtained with laparotomy. CONCLUSION This new technique made laparoscopic lower anterior resection possible to transect the lower rectum in the same way as is done with laparotomy.

Does radical resection improve the survival in patients with carcinoma of the gallbladder who are 75 years old and older

Radical resections have been reported to improve the surgical outcome for patients with carcinoma of the gallbladder, in recent years surgeons have had more opportunities to operate on elderly patients. We investigated whether the survival rate of aged patients who had radical resections were better than rates for those who had simple cholecystectomy. Of the 300 patients treated for carcinoma of the gallbladder between 1971 and 1999, 206 resected cases (except pancreaticoduodenectomy and hepatectomy) were divided into two groups: age 75 years or older, 54 patients (the older group), and age less than 75 years, 152 patients (the younger group). Clinical features and progression of the carcinomas did not differ between the two groups. In the older group, 22 patients (40.7%) had simple cholecystectomy, 32 (59.3%) had radical resections; in the younger group, 65 patients (42.8%) had simple cholecystectomy, and 87 (57.3%) had radical resection. None of the older patients who had radical resection died postoperatively. Postoperative survival was not different between the two groups. In the older group the 5-year survival rate for patients who had radical resections was better (60.9%) than the rate for those who had simple cholecystectomy (14.1%) (p=0.0098). Radical resection is effective for the aged patients with the carcinoma of gallbladder. On a rapporté que les résection radicales amélioraient le pronostic des patients atteints de cancer de la vésicule biliaire. Actuellement, on opère des patients de plus en plus âgés. Nous avons cherché à savoir si le taux de survie des patients âgés ayant eu une résection radicale était meilleur que celui de ceux qui ont eu une cholécystectomie simple. Parmi 300 patients traités pour cancer de la vésicule biliaire entre 1971 et 1999, 206 cas réséqués (exceptés les duodénopancréatectomies et les hépatectomies) ont été divisés en deux groupes: ceux âgés de 75 ans ou plus, 54 patients (le groupe «âgé»), et ceux âgés de moins de 75 ans, 152 patients (le groupe «jeune»). Les données cliniques et l’évolution des cancers ne différaient pas entre les deux groupes. Dans le groupe «âgé», 22 (40.7%) ont eu une cholécystectomie simple, 32 (59.3%) ont eu une résection radicale; dans le groupe «jeune», 65 (42.8%) ont eu une cholécystectomie simple alors que 87 (57.3%) ont eu une résection radicale. Aucun patient ayant eu une résection radicale n’est décédé après l’intervention. La survie postopératoire ne différaient pas entre les deux groupes. Dans le groupe «âgé», la survie à 5 ans pour les patients qui ont eu une résection radicale était meilleure (60.9%) que celle de ceux qui ont eu une cholécystectomie simple (14.1%) (p=0.0098). La résection radicale est efficace chez le patient âgé porteur de cancer de la vésicule biliaire. Según algunas publicaciones, la resección radical puede mejorar los resultados en pacientes con carcinoma de vesícula. En la actualidad, ante el incremento de pacientes añosos son más frecuentes estas intervenciones. Por ello, en este trabajo se pretende averiguar sí la tasa de supervivencia en estos enfermos, es mayor tras resección radical que tras la simple colecistectomía. Entre 1971 y 1999 se intervinieron 300 pacientes por padecer un carcinoma de vesícula; 206 casos fueron resecados (excepción hecha de las duodenopacreatectomías y hepatectomías) dividiéndose en dos grupos: grupo de viejos (≥ 75 años, n=54) y grupo de jóvenes (< 75 años, n=152). La clínica y la progresión del carcinoma fueron similares en ambos grupos. En el grupo de viejos: 22 (40.7%) fueron simplemente colecistectomizados y 32 (59.3%) sufrieron una resección radical. En el grupo de jóvenes: 65 (42.8%) fueron colecistectomizados y en 87 (57.3%) se practicó una resección radical. Ningún paciente añoso falleció en el postoperatorio. En ambos grupos, la supervivencia en el postoperatorio inmediato, fue similar. En el grupo de viejos, la supervivencia a los 5 años, tras resección radical, fue mayor 60.9% de los casos, que en los pacientes colecistectomizados (14.1%) (p=0.0098). Por tanto, la resección radical constituye el tratamiento de elección para pacientes añosos con cáncer de vesícula biliar.

The effect of dopamine on rat gastric motility.

SummaryThe inhibitory mechanism of dopamine (DA) on rat gastric motility was investigated in association with DA receptors. Gastric movement was assessed according to the method of Jacoby et al and was expressed with the system of Ludwick et al. (1968). DA inhibited gastric movement in both the corpus and antrum in a dose-dependent manner. Domperidone, a specific antagonist of DA2 receptor, suppressed DA-induced inhibition of gastric movement in a dose-dependent manner. SCH23390, a specific antagonist of DA1 receptor did not affect DA-induced inhibition of gastric movement. LY171555, a specific agonist of DA2 receptor, inhibited gastric movement in both the corpus and antrum in a dose-dependent manner. SKF38393, a specific agonist of DA1 receptor, did not affect gastric movement. These results indicate that DA plays an important role in the inhibitory regulation of gastric motility, through DA2 receptor but not DA1 receptor.

Inhibitory Effect of Peptide YY on Gastric Acid Output in Rats

The administration of peptide YY (PYY: 0.8, 1.6 and 3.2 nmol/kg/h, i.v.) to fasting rats inhibited not only baclofen (2 mg/kg, s.c.)-stimulated gastric acid output and gastric mucosal blood flow, but also pentagastrin (8 micrograms/kg/h, i.v.)-stimulated gastric acid output. PYY (3.2 nmol/kg/h) reduced baclofen-induced acid output more than pentagastrin-induced acid output, i.e., by 61.8 +/- 11.5% compared to 35.3 +/- 8.2%. PYY inhibited acetylcholine (ACh) release from cholinergic nerve endings of gastric body evoked by electrical transmural stimulation (ETS: 1 msec, 10 V, 3 Hz, 30 sec) by 47.2 +/- 3.5%. The mechanism of the inhibitory effect of PYY on gastric acid output seems to involve decreased gastric mucosal blood flow and reduced ACh release from cholinergic nerves.

An Approach to the Mechanism of Acute Ulceration in Obstructive Jaundice

Changes of noradrenaline (NA) and prostaglandin (PG) E2 in gastric mucosa and gastric wall blood flow (GWBF) were investigated after stress load in rats with obstructive jaundice. We found that water immersion and restraint stress more easily increased the ulcer index and decreased GWBF, corresponding to a decrease of the NA and PGE2 contents in the gastric mucosa, as the duration of jaundice increased. Administration of PGE2 reduced the increase of the ulcer index and the decrease of the GWBF and NA contents in the gastric mucosa. It is suspected that the rapid decrease of NA and PGE2 is connected with the rapid decrease of GWBF after stress load in obstructive jaundice, and we reached the hypothesis that both PGE2 and NA mutually regulate local GWBF.

The mechanism of acute gastric ulcer after induced hemorrhagic shock.

Changes in gastric mucosal blood flow were investigated for their relationship to gastric mucosal prostaglandin E2 (PGE2) and noradrenaline (NA) in rats with hemorrhagic shock. The results were as follows: 1) Gastric mucosal blood flow and NA decreased after hemorrhage. Gastric mucosal PGE2 initially increased after exsanguination and then markedly decreased. 2) Administration of NA before hemorrhage resulted in an increase of PGE2. However, the PGE2 value for animals receiving NA after hemorrhage was not different from that of non-NA-treated group. 3) Pre-treatment with PGE2 suppressed the reduction in both gastric mucosal blood flow and NA and the development of ulcer. These results suggest that the increase in gastric mucosal PGE2 in the early stage of shock might represent a phenomenon of adaptation by the adrenergic activation, and the decrease in PGE2 in the late stage might result from impaired synthesis of PGE2 due to persistent hypoxia and might be one of the possible factors in ulcer formation.

Effect of dopamine on prostaglandin E2 content in gastric mucosa

SummaryThe effects of dopamine (DA) on the prostaglandin (PG) E2 content of rat gastric mucosa was investigated. There was a 17.5% increase in gastric mucosal blood flow (BF) after administration of DA (5 μ/kg/min iv). After pretreatment with fusaric acid (FA), an antagonist of dopamine ß hydroxylase, DA increased BF by 27.8%. The PGE2 content in DA and DA + FA groups increased at rates of 45.8% and 42.4%, respectively. The PGE2 content in gastric mucosa after incubation following Basso’s method, increased in the DA, DA + FA and noradrenaline (NA) groups to 3.32±0.40 μg/g, 3.30±0.39 μg/g and 3.37±0.42 μg/g respectively. It is concluded that there are no differences in PGE2 content among the DA, DA + FA and NA groups. The mechanism by which PGE2 content increases after administration of DA is the direct action of DA and/or increasing BF. It is suspected that DA directly affects PGE2 synthesis, however the possibility that DA is metabolized to NA, which secondarily results in increased PGE2 synthesis, cannot be excluded.

Experimental Study of Vagotomy for Prevention of Stress Ulcer after Hepatectomy of Cirrhotic Livers Its Influence on Hepatic Regeneration

We experimentally studied the influence of vagotomy on hepatic regeneration in rats after hepatectomy of cirrhotic livers. In animals that underwent hepatectomy plus vagotomy the reduction in gastric pH was suppressed, but gastric mucosal blood flow was less than that in control animals that received hepatectomy alone. The suppression of 3H-thymidine uptake percentage and thymidine kinase activity after hepatectomy was more marked in animals treated with hepatectomy plus vagotomy than in controls treated with hepatectomy alone. Hepatic DNA level tended to be lower in animals treated with hepatectomy plus vagotomy than in controls. In animals treated with hepatectomy plus vagotomy, the peak level of the mitotic index was lower and the hepatic regeneration rate was evidently suppressed. These results suggest that it is not appropriate to apply vagotomy, during hepatectomy of cirrhotic livers, for the prevention of postoperative stress ulcer because it causes a marked reduction in gastric mucosal blood flow and suppresses hepatic regeneration.

An immunohistochemical study of glucagonoma conducted on the metastatic lymph nodes from a patient with recurrent metastatic glucagonoma: report of a case

In this report, we briefly present the case of a 67-year-old woman who developed recurrent glucagonoma with lymph node metastasis. An immunohistochemical study of the metastatic tumor revealed immunoreactivity of glucagon and protein kinase C (PKC)-α, -β, and -γ in the tumor cells, two types of which were seen by electron microscopy. One type had abundant secretory granules and mitochondria, while the other had few granules and mitochondria. Some granules were similar to typical A cell granules and others were atypical. An immunoelectron microscopic demonstration revealed PKC-α, -β, and -γ immunostaining in the cytoplasm of all the tumor cells, while some secretory granules had PKC immunostaining, and others had no immunostaining. Thus, it appears that metastatic glucagonoma and its associated granules are composed of two types of mature and immature cells or granules. As immunoreactivity of PKC-α and -γ was found in the tumor cells, but not in the normal A cells of the islets of Langerhans, the PKC subspecies α and γ, which are not present in normal pancreatic A cells, may exist in human glucagonoma cells.