[Indication and limitation of microwave coagulation therapy for stage IV-A hepatocellular carcinoma].

Patients with stage IV-A hepatocellular carcinoma have been considered to have dismal prognosis. However, among them there are many of patients with multiple carcinoma of multicentric origin, whose prognosis is not necessarily poor. For treatment of multiple carcinoma, preoperative evaluation for the malignant aggressiveness of each nodule, and for liver function impairment is essential. Although hepatic resection has a high curability, resection sometimes impair long term survival because of postoperative deterioration of liver function. In this point, heat ablation therapy such as microwave coagulation therapy is favorable treatment, and for some nodules at early stage heat ablation therapy would have a sufficient curability to achieve long term survival. Authors decide on the selection of treatment (resection or heat ablation therapy) according to preoperative evaluation for the malignant aggressiveness by diagnosis of tumor gross type, and for the degree of liver impairment by serum hyaruronic acid level.

Gastric stromal tumor with CD34 immunoreactivity--a case report.

Gastric stromal tumors are the most common mesenchymal tumors, and such submucosal mass lesions of the upper gastrointestinal tract occur frequently. A 54-year-old woman with no major complaint was admitted to our hospital for evaluation of a mass located between the stomach and the pancreas. Abdominal ultrasonography, computed tomography and endoscopic ultrasonography demonstrated a mass lesion which was located near the lesser curvature of the stomach. Selective left gastric arterial angiography revealed a hypervascular mass, and we diagnosed it as a leiomyosarcoma of the stomach. At laparotomy, there was a large solid mass 5 cm in diameter along the minor curvature of the stomach. Tumor resection with partial gastrectomy was performed, and the histological diagnosis was a gastric stromal tumor with CD34 immunoreactivity. We report a case of stromal tumor of the stomach with extramural growth and review the literature.

Gastric enterochromaffin-like-cell tumor with liver and splenic metastases.

We report a patient with gastric enterochromaffin-like-cell tumor with liver and splenic metastases. He was 68 years old and presented with major complaints of epigastric pain and weight loss. Under the diagnosis of gastric carcinoma with liver metastasis, total gastrectomy with splenectomy and lateral segmentectomy of the liver was performed. Intraoperative findings resulted in a diagnosis of adenocarcinoma T3N2P0H1, in stage IVa. Histological examination of the resected specimens showed a well differentiated neuroendocrine carcinoma (enterochromaffin-like-cell tumor) with liver and splenic metastasis which demonstrated high-grade lymphatic and vascular invasion. There was no lymph node metastasis. The tumor cells in the stomach, liver and spleen were immunoreactive for chromogranin A and Grimelius--positive. We review the literature, as well as presenting this case report.

Endocrine tumor of the pancreas--an evaluation of eighteen patients who underwent resection followed by long-term survival.

Tumors arising from the pancreatic endocrine (islet) cells represent a heterogeneous group of lesions. Some tumors present with well characterized syndromes, while others appear to be nonfunctioning. Eighteen patients with pancreatic endocrine tumors who received surgical treatment at Kurume University Hospital during a 24-year period were reviewed. There were 10 patients with nonfunctioning tumors including 3 patients with benign tumors, and 8 patients with insulinomas. No patients had multiple endocrine neoplasms. Location of the pancreatic tumor was determined preoperatively in 83.3% of the patients. Immunohistochemical analysis of the resected specimens showed multi immunoreactivity to gut hormones among benign lesions and one malignant lesion, whereas malignant lesions showed no or mono immunoreactivity except in one case. In this series, there were no characteristic immunohistochemical findings in the tumors. Both patients with malignant and benign lesions have good prognoses if the main tumors and metastatic lesions are removed.

A resected case of pancreatic metastasis from primary renal cell carcinoma.

A 71-year-old man, who had received a right nephrectomy for a primary renal cell carcinoma 8 years earlier, and had two years later received a distal gastrectomy for duodenal ulcer, was admitted. In the subsequent clinical course, a solitary low echographical tumor was found in the pancreas. Abdominal computed tomography revealed a tumor of low density area, and celiac angiography revealed a hypervascular tumor stain of the pancreas. From the above findings, a diagnosis of pancreatic tumor was made, and a distal pancreatectomy was performed. Examination of the resected tissues confirmed the presence of a solitary tumor in the pancreatic tail. Histologically, the tumor corresponded to the initial renal cell carcinoma and pancreatic metastasis of renal cell carcinoma was diagnosed. We report a resected case of such a metastasis and review the literature.

A long-term survival patient with advanced gallbladder cancer massively metastasizing to the liver.

A case of gallbladder carcinoma was reported. A 42-year-old woman was admitted with epigastralgia. Abdominal ultrasonography, computed tomography, and other diagnostic modalities suggested gallbladder carcinoma with multiple liver metastases. These findings indicated no surgical procedure because of the advanced nature of her disease. After the hepatic arterial chemoinfusion therapy, her multiple liver metastatic lesions showed a decrease in size and number. Therefore, extended left lobectomy of the liver with gallbladder and bile duct resection were performed. Five years after initial operation, a solitary liver metastatic lesion (S5) was diagnosed by ultrasonography. Partial resection of the liver was performed for the liver metastasis, and her postoperative recovery was uneventful and had a good follow-up course. One year after the second operation bone metastases occurred, therefore, peroral administration of UFT (Tegafur + Uracil) and radiation therapy for the metastatic lesions of sternum and lumbar vertebra (L1) were performed.

A so-called carcinosarcoma of the gallbladder in a patient with multiple anomalies--a case report.

The patient was a 65-year-old woman with a chief complaint of right upper quadrant pain. Under the diagnosis of gallbladder tumor, preduodenal portal vein and absence of the pancreatic tail, cholecystectomy was performed. Intraoperative findings resulted in a diagnosis of gallbladder tumor, absence of the pancreatic tail, presence of preduodenal portal vein, and malrotation of the intestine. Histological examination of the resected specimens showed a so-called carcinosarcoma. Carcinosarcoma of the gallbladder is a rare tumor of the hepatobiliary region. The present case differs from previously reported cases in its presentation with multiple anomalies including the presence of preduodenal portal vein. Many cases of preduodenal portal vein in an association with duodenal stenosis in children have been reported, but reports of cases of preduodenal portal vein in adult patients are rarely seen in the literature.

Nonfunctioning islet cell carcinoma--a twenty-one years survival case after distal pancreatectomy.

A case of nonfunctioning islet cell carcinoma was reported. A 40-year-old woman was admitted with epigastralgia. Abdominal angiography and other diagnostic modalities suggested pancreatic malignancy. After distal pancreatectomy, histopathological study revealed her pancreatic tumor to be a nonfunctioning islet cell carcinoma. Fourteen years later, postoperative computed tomographic examination (CT) detected the recurrence of para-aortic lymph node metastases. Five years later, distal gastrectomy was performed to control bleeding from a gastric ulcer. Twenty-one years after the original operation, she died because of underlying metastatic carcinoma. In this case, slow growth and a low grade malignancy were characteristic. Operative removal of the tumor would be the treatment of choice even if metastatic lesions existed.

The characteristics of specific IgG to phthalic anhydride (PA)-albumin conjugate.

Phthalic anhydride (PA), used in the chemical industry, binds to proteins and causes allergic reactions. It is important to study the characteristics of antibody to PA-protein. We produced specific IgG against PA-rabbit serum albumin (RSA) by administering subcutaneous injections of PA-RSA conjugate to two rabbits. Both rabbits' sera had high titers of IgG not only to PA-RSA but also to PA-human serum albumin (HSA) and HSA. In enzyme-linked immunosorbent assay (ELISA) and ELISA HSA inhibition, specific IgG to PA-HSA revealed cross-reactivity to three other phthalyl anhydride conjugates, hexahydrophthalic anhydride (HHPA)-HSA, methylhexahydrophthalic anhydride (MHHPA)-HSA, and methyltetrahydrophthalic anhydride (MTHPA)-HSA, in both sera. Titers of IgG to HHPA-HSA, MHHPA-HSA, and MTHPA-HSA were not significantly different. On affinity chromatography, highly specific IgG to PA hapten alone was purified. In the serum not binding to PA column, specific IgG to PA-HSA was significantly less than in original serum, but levels of specific IgG to other phthalyl anhydride-HSA were unchanged. Rabbits immunized with PA-RSA produced at least two types of IgG: one is to PA hapten alone and the other may be against new antigenic determinants (NADs) on HSA.

Male fertility in rats treated with etretinate for 4 weeks.

The toxicity of Etretinate, a retinoid compound, on the male reproductive system was studied in male rats. The drug was administered for four weeks at the dose levels of 0 (control: Vehicle, Peanut oil), 5 and 25 mg/kg/day. The animals were then allowed to mate, and their male reproductive functions and organs were examined in detail. No significant changes due to toxicity were observed in male reproductive functions and organs in the 5 mg/kg/day group after the 4-week treatment. In contrast, males in the 25 mg/kg/day group showed drug-related changes in their reproductive performance (decrease of mating ability and fertility rate), testosterone blood level, sperm head counts, sperm viability and number in the caudal epididymis, organ weight and in the histopathology of their reproductive organs (atrophy of seminiferous tubules, necrosis of spermatocytes and spermatids, vacuolation of nuclei of spermatocytes and spermatids). Even though Etretinate belong to the retinoid group of compounds, the changes seen in the 25 mg/kg/day group were almost the same as those observed in Vitamin A-deficient animals. In conclusion, there is a correlation between changes due to toxicity observed for parameters of male fertility and for histopathological evaluation of the testis of rats that receiving high dose, treatment with Etretinate for 4 weeks.

Mobilization of gastric histamine during repeated administration of a proton potassium adenosine triphosphatase inhibitor in intact and antrectomized rats.

Intact and antrectomized female rats were treated with the potent proton pump inhibitor, E3810 (daily 40 mg/kg weight, s.c.) for 4 weeks. Plasma gastrin concentration and urinary excretion of N-terminal big gastrin increased until day 14 and persisted at a high level in intact rats treated with E3810, but did not increase in antrectomized rats. Urinary excretion of histamine increased progressively and reached 7 times the control value following 4 weeks of treatment with E3810 in intact rats, but not in antrectomized rats. At the termination of the treatment, the endocrine cell density in the oxyntic mucosa of intact rats had increased by 85% with increased histamine content and elevated histidine decarboxylase activity, while antrectomized rats showed a low histamine level and low histidine decarboxylase activity. Administration of gastrin-17 I (10 micrograms/kg weight, sc) itself caused a significant increase in urinary excretion of histamine, which was inhibited by the specific gastrin receptor antagonist, L-365,260. These results suggests that the massive urinary excretion of histamine caused by the treatment with E3810 reflects gastrin-induced mobilization of gastric histamine and that neither E3810 itself nor E3810-induced luminal pH elevation has direct effects on mobilization of oxyntic mucosal histamine.

Inhibition of gastrin-stimulated enterochromaffin-like cell proliferation and mucosal histamine production in the rat stomach by the somatostatin analogue octreotide.

The effect of octreotide, a potent and long-acting analogue of somatostatin, on gastrin-stimulated proliferation and function of enterochromaffin-like (ECL) cells were examined in rats. Animals were divided into four groups and each group was continuously infused with saline, octreotide alone (40 micrograms/kg per day), gastrin alone (60 nmol/kg per day), or octreotide (40 micrograms/kg per day) plus gastrin (60 nmol/kg per day) respectively for 9 days via osmotic minipumps. Gastrin induced the increase of the bromodeoxyuridine labeling index and density of oxyntic mucosal ECL cells as well as oxyntic mucosal histidine decarboxylase activity. Octreotide completely abolished the gastrin-induced increases in the labeling index and density of ECL cells and oxyntic mucosal histidine decarboxylase activity. These results indicate that octreotide inhibits gastrin-stimulated proliferation of ECL cells and histamine production by these cells.

Helicobacter pylori increases gene expression of hepatocyte growth factor in human gastric mucosa.

Helicobacter pylori (H. pylori) induces hyperproliferation of the gastric mucosa. This study was designed to clarify whether H. pylori infection is involved in the gene expression of hepatocyte growth factor (HGF), a potent stimulator of cell proliferation in gastric mucosa. Levels of HGF mRNA were determined by a reverse transcription-polymerase chain reaction in endoscopic gastric biopsy specimens from 9 control subjects and 9 patients with H. pylori infection. In patients with H. pylori infection, levels of HGF mRNA in gastric mucosa were significantly higher than those in control subjects. HGF mRNA levels in patients with H. pylori infection were correlated with the severity of gastric mucosal inflammation. Our observations indicate that H. pylori infection increases the expression of HGF gene in gastric mucosa probably through the mucosal inflammation.

Determination of histidine decarboxylase mRNA in various rat tissues by the polymerase chain reaction.

Histidine decarboxylase (HDC) mRNA in various rat tissues were quantitated by using a reverse transcription-polymerase chain reaction (RT-PCR) in which a mouse mRNA was used as an internal standard. The stomach HDC mRNA level was the highest followed by the brain, skin, jejunum, spleen and liver. There was no measurable HDC mRNA in the kidney. The stomach HDC activity was also the highest followed by the brain, skin, spleen, jejunum, liver and kidney. A significant correlation (r = 0.940, p < 0.0001) was observed between the HDC mRNA levels and HDC activities in these tissues. We have also examined the HDC mRNA levels in fasting rats and found that HDC mRNA levels in the stomach were reduced after the 48-hr-fasting with the decrease in HDC activities. These observations indicate that there may exist a gene regulation, at least at the basal level, for the HDC activities in the rats.

Interleukin-1 beta inhibits gastric histamine secretion and synthesis in the rat.

Interleukin-1 beta (IL-1 beta) is the most potent inhibitor of gastric acid secretion known at present. Although histamine has been shown to be an important mediator of gastric acid secretion, the effect of IL-1 beta on gastric histamine mobilization has not been studied. In the present study, the effects of IL-1 beta on gastric acid secretion and gastric histamine mobilization were investigated in conscious rats with both gastric and vesical fistulas. IL-1 beta (5 micrograms/kg iv) significantly inhibited basal acid secretion but did not affect basal urinary histamine excretion and fundic histidine decarboxylase (HDC) activity. Gastrin-17-I (1 nmol.kg-1.h-1) caused a marked increase in acid secretion, urinary histamine secretion, and fundic HDC activity. IL-1 beta (5 micrograms/kg iv) completely inhibited gastrin-induced acid secretion and partially inhibited urinary histamine excretion and fundic HDC activity. Pretreatment with indomethacin (10 mg/kg ip) partially reversed the inhibitory effects of IL-1 beta on gastrin-stimulated fundic HDC activity and acid secretion. These findings indicate that IL-1 beta inhibits gastric histamine mobilization through both prostaglandin-dependent and prostaglandin-independent pathways. Furthermore, it is suggested that the inhibitory action of IL-1 beta on gastric acid secretion is mediated by the inhibition of gastric histamine mobilization.

Purification and characterization of diamine oxidase (histaminase) from rat small intestine.

Diamine oxidase (DAO) was purified to homogeneity from rat small intestine, and its biochemical and immunochemical properties were studied. DAO was suggested to be a dimer of a 92 kDa subunit, and its isoelectric point was found to be 6.0. Histamine, putrescine, N tau-methylhistamine, and cadaverine were good substrates, with Km values ranging from 9.4 to 16.0 microM. Spermine and spermidine were not substrates. Both an immunoprecipitation study and Ouchterlony's double diffusion test involving antiserum against the purified DAO showed that the immunological properties of the DAOs from rat small intestine, thymus, and placenta were identical. Among small intestinal DAOs from different species, this antibody reacted to the guinea pig enzyme as strongly as to the rat enzyme, but the reaction was much weaker to the mouse enzyme than to the rat enzyme. The DAOs from rabbit and dog small intestine, pig kidney, and human placenta showed no reactivity toward this antibody.

Expression and characterization of the bovine histamine H1 receptor in cDNA-transfected C6 astroglioma cells.

Rat C6 astroglioma cells (C6-bH1R cells) expressing cloned bovine histamine H1 receptors were established by transfection with a vector (pEF-BOS-bH1R) which carried a 2.7-kbp EcoRI fragment of the bovine H1 receptor cDNA [Yamashita, M. et al. (1991) Proc. Natl. Acad. Sci. USA 88, 11515-11519]. The cloned bovine H1 receptor in C6-bH1R cells was characterized by three established criteria: the [3H]mepyramine binding assay, the accumulation of inositol phosphates induced by histamine, and histamine-induced elevation of intracellular Ca2+ concentration ([Ca2+]i). The accumulation of inositol phosphates induced by histamine was time- and dose-dependent. The accumulation of inositol trisphosphate was biphasic with a prompt increase to the maximal level, followed by a sustained submaximal level. The histamine-induced accumulation of inositol phosphates was suppressed by phorbol ester, but not by pertussis toxin. Results from the [3H]-mepyramine binding assay and histamine-induced elevation of [Ca2+]i were characteristic of H1 receptors. Several compounds among tricyclic antidepressants, neuroleptics, and serotonin antagonists showed affinities to the cloned bovine H1 receptor with Ki values similar to reported values. Histamine neither induced cAMP accumulation nor attenuated forskolin-induced cAMP accumulation in C6-bH1R cells. C6-bH1R cells are particularly useful for studying the H1 receptor-mediated astroglial cell functions.

Tissue distribution of histamine N-methyltransferase-like immunoreactivity in rodents.

The rat kidney histamine N-methyltransferase was purified to homogeneity from Escherichia coli transfected with its recombinant cDNA. An antiserum to the enzyme was raised in rabbit by immunization with the purified protein. Western blot analysis of rat tissues with the antiserum revealed a band with identical mobility to that of purified enzyme in the extracts of kidney, jejunum, and brain, where the enzyme activity was detected. The antiserum cross-reacted with a 32K protein in mouse liver, brain, stomach, kidney and lung, and a 33K protein in guinea pig brain, stomach jejunum, spleen, lung, and kidney. The intensity of the staining in western blotting correlated well with the enzyme activity in all the tissues in these three species, suggesting that our antiserum is useful for quantifying histamine N-methyltransferase protein in rodent tissues.

Role of nucleosides and nucleotide mixture in intestinal mucosal growth under total parenteral nutrition.

The preventive effect of a mixture of nucleosides and a nucleotide (OG-VI) on total parenteral nutrition (TPN)-associated gut mucosal atrophy was investigated. Male Wistar rats were randomly divided into two groups. The TPN group (n = 11) received a standard TPN diet (250 kcal and 1.78 g nitrogen.kg-1.day-1) for 6 days; the TPN + OG-VI group (n = 10) received OG-VI (2.5 ml.kg-1.day-1) in addition to the standard TPN solution for 6 days. To obtain information on a normal fed condition of the intestine, another 10 rats were maintained on oral rat chow for 6 days. Compared with the TPN group, mucosal wet weights in the jejunum (22.8 +/- 1.8 vs. 20.5 +/- 2.0 mg/cm) and the ileum (19.4 +/- 2.2 vs. 16.8 +/- 2.3 mg/cm) were significantly greater in the TPN + OG-VI group. Likewise, diamine oxidase activities in the jejunum (13.7 +/- 4.27 vs. 8.02 +/- 3.40 nmol.min-1.cm-1) and the ileum (33.9 +/- 6.89 vs. 25.9 +/- 7.93 nmol.min-1.cm-1) were significantly higher in the TPN + OG-VI group. Moreover, the bromodeoxyuridine labeling index in the TPN + OG-VI group (36.9 +/- 4.30%) was significantly higher than in the TPN group (31.0 +/- 3.03%). The addition of OG-VI to the standard TPN diet improved mucosal growth and maturity by increasing the proliferating activity of crypt cells. External provision of purines and pyrimidines may be necessary to sustain mucosal function during TPN.

Somatostatin inhibits gastrin-induced histamine secretion and synthesis in the rat.

Somatostatin is a potent inhibitor of gastric acid secretion. However, the effect of somatostatin on gastric histamine secretion and synthesis has not been well understood, despite the fact that histamine plays a key role in the regulation of gastric acid secretion. This study was designed to determine the effect of somatostatin on gastric histamine mobilization and acid secretion in conscious rats. In conscious rats with a gastric fistula, a 4 h intravenous infusion of gastrin-17 I (1 nmol/kg/h) evoked a marked increase in fundic histidine decarboxylase activity (the sole histamine-forming enzyme) and reduced fundic histamine content with a concomitant increase in gastric acid secretion. Somatostatin-14 (10 nmol/kg/h) significantly inhibited gastrin-induced gastric acid secretion and fundic histidine decarboxylase activity and prevented a gastrin-induced decrease in fundic histamine content. In conscious rats with a vesical fistula, somatostatin-14 (10 nmol/kg/h) significantly inhibited the urinary histamine excretion induced by a gastrin-17 I (1 nmol/kg/h) infusion. These findings suggest that the inhibitory action of somatostatin on gastrin-induced acid secretion is mediated by the inhibition of histamine mobilization.