Clinical and endoscopic characterization of depressed gastric adenoma.

BACKGROUND AND STUDY AIM: Depressed gastric adenoma remains poorly characterized because it is rare, and is infrequently detected by endoscopy. The aim of this study was to elucidate clinical and endoscopic characteristics of depressed adenoma of the stomach. PATIENTS AND METHODS: 95 consecutive patients who underwent endoscopic resection of gastric adenomas were studied. Gastric adenomas, diagnosed according to the Vienna classification, were endoscopically classified into two types: depressed and protruding adenomas. In order to clarify endoscopic features of gastric adenomas, we performed indigo carmine chromoendoscopy as well as magnifying endoscopy with narrow band imaging, which yields clear images of mucosal microvasculature. RESULTS: 12% of 100 gastric adenomas resected from 95 patients were depressed adenomas. Age and gender were comparable between patients with each type. Depressed adenomas (15.9 +/- 6.2 mm) were significantly larger in diameter than protruding adenomas (10.6 +/- 8.0 mm) (P = 0.01). Half of depressed adenomas were reddish in color, whereas only 18% of protruding adenomas were reddish. Magnifying endoscopy with narrow band imaging showed that 71% of depressed adenomas had a regular ultrafine network pattern of mucosal microvasculature, which was not seen in protruding adenomas. Intramucosal carcinomas were more frequently found in depressed adenomas (25%) than in protruding adenomas (4.5%). CONCLUSIONS: In comparison with protruding adenomas, depressed adenomas were rare and appeared endoscopically as large and reddish with a specific regular ultrafine network pattern of mucosal microvasculature. Depressed adenomas should be endoscopically resected because intramucosal carcinomas were found in a quarter of them.

Common hepatic artery aneurysm branching from the superior mesenteric artery. Report of a case.

A 58-year-old man was notified as having a mass in the head of the pancreas at medical checkup on September 26, 2000. He was admitted to our department after being diagnosed as having an aneurysm in the common hepatic artery, branching from the superior mesenteric artery (SMA), based on selective SMA angiography. From an abdominal midline incision, we were able to reach his common hepatic artery aneurysm (CHAA) by mobilizing the pancreas through the route lateral to the greater curvature of the stomach. This aneurysm arose in the common hepatic artery immediately after branching from the SMA. After proximal and distal control of the SMA and common hepatic artery, the aneurysm was incised and the distal hepatic artery was anastomosed end to side to the SMA. The patient had an uneventful postoperative course.

Expression and distribution of transcripts for sonic hedgehog in the early phase of fracture repair.

Localization and expression of mRNAs for sonic hedgehog (Shh) at a fracture site in the early phase postfracture were investigated by in situ hybridization and reverse transcription and polymerase chain reaction (RT-PCR). A closed fracture was made in the midshaft of the right tibia of 5-week-old ICR mice, and fractured sites were harvested prefracture (day 0) and on days 2 and 12. In situ hybridization revealed that transcripts for Shh were not detected on day 0, but they were detected in proliferating callus-forming cells in the periosteum and the surrounding tissue, and in the medullary cavity prior to apparent new cartilage and bone formation. Gli 1 (a signaling mediator for Shh) and bone morphogenetic protein-4 transcripts were colocalized with those for Shh transcripts on day 2. The RT-PCR showed that Shh mRNA was detected in the PCR product from day 2, but not from days 0 and 12. These findings are the first description about the activation of Shh gene in the early postfracture reaction.

Immunohistochemical detection of parathyroid hormone-related peptide, Indian hedgehog, and patched in the process of endochondral ossification in the human.

Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (Ihh), and patched (Ptc; a receptor for Ihh) were immunolocalized in tissue undergoing endochondral ossification in the human. PTHrP, Ihh, and Ptc were immunolocalized in prehypertrophic and hypertrophic chondrocytes in mature cartilage matrix. PTHrP and Ptc were immunostained in proliferating chondrocytes and perichondrial cells, whereas Ihh was not. PTHrP, Ihh, and Ptc showed positive immunostaining in osteoblasts in the bone-forming area. In the bone resorption site, PTHrP was immunolocalized in osteoclasts, whereas Ihh and Ptc were not. The present findings indicated that PTHrP, Ihh, and Ptc were associated with the process of endochondral ossification, and suggested the possible involvement of Ihh and PTHrP signaling in the regulation of proliferation and hypertrophy of chondrocytes in human chondrogenesis.

[A case with lung metastasis of osteosarcoma occurred 21 years after the operation of osteosarcoma on left tibia].

The patient was a 38-years-old woman. A chest X-ray film demonstrated the presence of an abnormal lesion. Her past history included osteosarcoma on the left tibia for which she received amputation of the left inferior limb at 17 years of age without any relapse thereafter. Considering that the patient might have lung metastasis of osteosarcoma on the basis of lung biopsy performed under CT guide, and then a tumor was removed under the thoracoscope. The tumor, 2.8 x 2.2 x 2.1 cm in size, was located right under the pleura at left S10 with its inside being filled up with fragile necrotic tissues. When compared pathohistologically with the primary lesion of osteosarcoma which had occurred 21 years before, the lung tumor was almost identical in terms of the tumor cell morphology but had a higher cell density without evidence of osteoid formation. The diagnosis of lung metastasis of osteosarcoma was established on the basis of the clinical course and the immunohistochemical staining. It is extremely rare case that osteosarcoma recurs in the form of lung metastasis 21 years after the operation of primary lesion. We report this case as a valuable one to identify the prognosis of osteosarcoma and the development mechanism of lung metastasis.

[Lobectomy of two or more lobes in patients with lung cancer].

We clinically examined patients who had undergone resection of two or more lobes for lung cancer. The subjects were 50 patients (25 who underwent pneumonectomy and 25 bilobectomy) who underwent lobectomy of two or more lobes from among those with primary non-small cell lung cancers in our hospital between 1975 and 1999; these individuals were assigned to Group A, and compared with 166 patients with lobectomy in Group B. The five-year survival rate was 27.7% in Group A, which differed significantly from the rate of 55.6% in Group B (p < 0.01, Kaplan-Meier method with log-rank test). The percentage of Stage I patients was 34% (17 patients) in Group A and 60.2% (100 patients) in Group B: this difference was significant (chi 2 test, p < 0.01). There were more patients with advanced cancer in Group A than in Group B. However, the five-year survival rates of Stage I patients were 52.4% in Group A and 77.6% in Group B, and significantly different (p < 0.05). In a comparison with respect to histological type, the five-year survival rates also differed significantly between Group A and B (p < 0.01 for adenocarcinoma, p < 0.05 for squamous cell carcinoma, with higher values in Group B for both). Resection of two or more lobes was indicated based on infiltration of the main tumor into adjacent lobes in 19 patients (38%), infiltration of lymph node metastasis into a bronchus or pulmonary artery in 14 (28%), direct infiltration of the main tumor into a bronchus in 10 (20%), and for other reasons in 7 (14%). The five-year survival rates for these groups were 15.8, 22.1, 54 and 42.9%, respectively. There was a significant difference between the patients with infiltration of cancer into adjacent lobes and those with direct infiltration into a bronchus (p < 0.05). The prognosis of patients with resection of two or more lobes was poorer than that of patients with lobectomy even in Stage I. In particular, infiltration of cancer into adjacent lobes accompanied lymph node metastasis in more than 50% in cases, and appeared to suggest a poor prognosis.

[A case of G-CSF-producing large cell carcinoma of the lung with gastric metastasis].

We report a rare surgically-treated case of G-CSF-producing large cell carcinoma of the lung with gastric metastasis. A 65-year-old male was admitted to our hospital because of fever, anemia and epigastralgia. Chest X-ray examination and CT scanning revealed a round mass shadow (8 cm) in contact with the chest wall in the right upper lung field and metastasis to the mediastinal lymph nodes. Laboratory examination showed a WBC of 16,800/mm3, CRP of 11.6 mg/dl, and a serum G-CSF of 90 pg/ml. Upper gastrointestinal series and gastroscopy showed an ulcerating submucosal tumorous lesion in the pyloric antrum. The lung carcinoma was treated by right upper lobectomy with chest wall resection. After 1 month, gastrectomy was performed. After the operation, the WBC normalized, and the CRP and serum G-CSF levels decreased. Histopathological examination demonstrated a poorly differentiated large cell carcinoma in the lung and a metastatic lesion in the stomach. Immunohistochemical staining with anti-G-CSF mono-clonal antibody showed negative results in the lung but positive results in the stomach. He was discharged 3 weeks after gastrectomy but died of aggravation of the general condition associated with local recurrence in the chest wall 2 months after discharge.

Effects of dehydroepiandrosterone on mitogen-activated protein kinase in human aortic smooth muscle cells.

The objective of the present study was to determine whether dehydroepiandrosterone (DHEA) modifies growth factor-induced mitogen-activated protein kinase (MAPK) activation, based on our previous study demonstrating that DHEA attenuates fetal calf serum-induced proliferation in human male aortic smooth muscle cells (human male aortic SMCs). Human male aortic SMCs were used for this study. Platelet-derived growth factor-BB (PDGF-BB), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), but not insulin-like growth factor-1 (IGF-1), stimulated MAPK activity. Only MAPK activation induced by PDGF-BB was reduced by pretreatment with DHEA, although DHEA did not affect the MAPK activation induced by EGF or bFGF. The basal and PDGF-stimulated MAPK activity were decreased by two types of cyclic AMP (cAMP) elevating agents and increased by cAMP-dependent protein kinase (PKA) inhibitor in human male aortic SMCs, suggesting that cAMP regulates MAPK negatively. The intracellular cAMP was increased by PDGF-BB. The increase of cAMP by PDGF-BB was augmented by pretreatment with DHEA, although DHEA alone did not affect cAMP. Neither EGF nor bFGF affected cAMP with and without DHEA pretreatment. Secretion of PGE2 induced by PDGF was augmented by pretreatment with DHEA. Stimulatory effects of DHEA on the production of PGE2 and cAMP were partially canceled by aromatase inhibitor and completely canceled by indomethacin or selective inhibitor of cyclooxygenase-2. These results suggest that DHEA inhibited MAPK activation induced by PDGF-BB via PGE2 overproduction and subsequent cAMP-dependent pathway in human male aortic SMCs.

Synthesis and antitumor activities of novel 6-5 fused ring heterocycle antifolates: N-[4-[omega-(2-amino-4-substituted-6,7-dihydrocyclopenta [d]pyrimidin-5-yl)alkyl]benzoyl]-L-glutamic acids.

Novel antifolates with a 6-5 fused ring system, 6,7-dihydrocyclopenta [d]pyrimidine, (3a,b and 4a,b) were synthesized on the basis of combined modification of the heterocycle and bridge regions of the folate molecule. The synthetic method involves (1) synthesis of key intermediates of tert-butyl 4-[omega-(2-substituted-3-oxocyclopentanyl) alkyl]benzoates (8a,b and 9a,b) by a carbon-carbon radical coupling of tert-butyl 4-(omega-iodoalkyl)benzoates (7a,b) with 2-substituted-2-cyclopenten-1-ones (5 and 6) utilizing tributyltin hydride, (2) cyclization of either the methyl enol-ethers derived from the 2-cyanocyclopentanones (8a,b) or the 2-(methoxycarbonyl)cyclopentanones (9a,b) themselves by treatment with guanidine which leads to 6,7-dihydrocyclopenta [d]pyrimidines with a 4-(tert-butoxycarbonyl)phenylalkyl group (11a,b and 14a,b), (3) deprotection to the corresponding carboxylic acids (12a,b and 15a,b), and (4) amidation with diethyl glutamate and deesterification. Potent dihydrofolate reductase inhibition and highly potent cell growth inhibition were found with 2,4-diaminopyrimidine-fused cyclopentene compounds containing the trimethylene (3a) or ethylene bridge (3b) but not with the corresponding 2-amino-4-hydroxy analogs (4a,b). Compounds 3a and 3b were more growth inhibitory to several tumor cell lines (P388, colon 26, colon 38, and KB) than was methotrexate, with 3a being the most potent. Both 3a and 3b gave increases in the lifespan of P388 leukemic mice comparable to that observed with MTX. Both compounds were therapeutic against colon 26 colorectal carcinoma in mice. Compound 3a was highly effective against LC-6 non-small cell lung carcinoma in nude mice.

Rat strain variations in liver cytosolic DT-diaphorase activity and possible significance of the trait in carcinogenesis by azo dyes.

1. Strain variations among female rats in terms of cytosolic DT-diaphorase activity were studied in liver, heart and glandular stomach tissues with or without administration of 3-tert-butyl-4-hydroxyanisole (BHA). 2. BHA induced liver DT-diaphorase activity in all strains examined, and both the basal and induced activities varied according to strain. Among the five strains tested, Brown Norway (BN) and Sprague-Dawley (SD) rats showed relatively high levels of enzyme activity in the liver, whereas Fischer (F344) rats showed a relatively low level of activity. Results of examination of Fischer-BN-F1 rats indicated that a lower level of liver DT-diaphorase activity was inherited essentially as a dominant trait. 3. Liver DT-diaphorase activity in male rats was significantly lower than in female rats. Small strain variations of the activity, if any, were observed in the heart and stomach cytosolic fractions with or without induction by BHA. The magnitude of induction by BHA was also small, if any, in heart and stomach cytosolic fractions. 4. From these and other observations, we discussed the differences between rats and mice in these strain and tissue variations of DT-diaphorase activity, and also the possible significance of liver DT-diaphorase activity in carcinogenesis by azo dyes.