Yoshifumi Yokoyama

Injection-incision–assisted snare resection of large sessile colorectal polyps☆☆☆★★★♢

BACKGROUND It can be difficult, even for experienced endoscopists, to completely remove large sessile colorectal polyps. We attempted to remove large sessile colorectal polyps without complication and residual tumors. METHOD Our new technique is characterized by submucosal pre-injection with a large volume of saline solution and then circumferential incision outside the lesion before resection using a special needle-tipped snare. The mean size of 33 polyps (including 9 elevated sessile, 20 flat nodular [villous], and 4 flat sessile polyps), was 4.0 cm (range, 3.0-8.5 cm). RESULTS Twenty-five (76%) were resected piecemeal and the remainder as a single specimen. Mild to moderate bleeding occurred in 3 (9.1%), but there was no clinically significant bleeding or perforation. No residual or recurrent tumors were recognized. Invasive carcinoma was revealed most frequently (44%) in elevated sessile polyps; none occurred in flat nodular polyps. CONCLUSION Our removal technique appears to be safe and effective. Flat nodular polyps of any size are a particularly good indication for removal by this technique.

Increased intake of n-3 polyunsaturated fatty acids elevates the level of apoptosis in the normal sigmoid colon of patients polypectomized for adenomas/tumors

To clarify preventive effects of n-3 polyunsaturated fatty acids (PUFAs) against colorectal carcinogenesis, we performed a dietary intervention in patients polypectomized for colorectal adenomas/tumors. For the former the following dietary advice was given: (1) decrease intake of fat from 30 to 20% of the total; (2) decrease consumption of n-6PUFAs containing foods, and increase intake of n-3 PUFAs for 2 years. For the comparison group only decreased intake of fat (30-20%) was recommended. Samples of normal sigmoid colon mucosa, obtained by colonoscopic check once a year during the intervention period, were used to investigate COX-2, cell proliferation (Ki67 expression), p53, Bcl-2 and Bax by immunostaining and determine the apoptosis index (AI) by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) in 21 and 20 patients in experimental and comparison groups, respectively, who completed the 2 years of the intervention. After 24 months, the AI and positive cells of Bax and the ratio of Bax/Bcl-2 in normal sigmoid colon mucosa for the experimental group was significantly increased, whereas this change was not found in comparison group. These observations demonstrated for the first time that increased intake of n-3 PUFAs promotes apoptosis of normal colon mucosa in human which is related to effect on Bax or the balance of Bax and Bcl-2.

Physiological concentrations of human epidermal growth factor in biological fluids: use of a sensitive enzyme immunoassay

A sandwich enzyme immunoassay for epidermal growth factor (EGF) has been developed which measures EGF concentrations in serum, urine, saliva, gastric and pancreatic juices without pretreatment. Sensitivity for human EGF is 500 fg/tube. Serum EGF concentration in normal males and females is 780 and 604 pg/ml, respectively. Urinary human EGF is 51.3 ng/mg creatinine for males, and 68.3 ng/mg creatinine for females. The difference is not significant, and no correlation between serum and urinary concentrations exists, but serum concentration changes with age. The highest concentration is seen up to 9 years of age, suggesting that EGF promotes cell proliferation during growth.

Intracystic hemorrhage of a simple liver cyst mimicking a biliary cystadenocarcinoma

Simple liver cysts are rarely complicated by intracystic hemorrhage. We encountered a case of simple liver cyst that was morphologically similar to biliary cystadenocarcinoma, which was complicated by asymptomatic intracystic hemorrhage and successfully treated by right lobectomy. A large cystic lesion of the liver was detected in a 57-year-old woman during a mass screening health check. Abdominal ultrasonography (US) revealed that the cystic lesion, containing many hyperechoic papillary structures, occupied almost the entire region of the right hepatic lobe. In addition, a round mural nodule, measuring approximately 5 cm in diameter, was detected in the cystic wall. Abdominal computed tomography (CT) revealed that the inner part of the cystic lesion showed homogeneous low density, but CT did not show the round nodule detected by US. On T1-weighted sequence of magnetic resonance imaging (MRI), the lesion showed homogeneous high signals, together with a low-signal tumorous lesion in the cystic wall. T2-weighted sequence of MRI showed unhomogeneous high signals, together with high signals in the tumorous part. These findings did not exclude the possibility of a malignant cystic tumor, such as biliary cystadenocarcinoma. Therefore, right lobectomy was performed. Histological examinations of resected tissue specimens revealed that the lesion was a liver cyst containing a large amount of blood clot, and that the tumorous lesion detected by US and MRI was a large mass of blood clot which was partly liquefied. This case indicates the diagnostic importance of the morphological discordance between CT and US or MRI findings for liver cyst containing a large amount of blood clot.

Complement plays an essential role in shock following intestinal ischaemia in rats

Intestinal ischaemia lasting more than 30 min in rats causes fatal systemic shock. Systemic shock was suppressed by preadministration of cobra venom factor (CVF), which reduced the serum complement to less than 5% of the normal level, indicating that complement is involved in the syndrome. After complement activation, anaphylatoxins such as C3a and C5a are generated, and their activity is restricted by carboxypeptidases which remove C‐terminal arginine from such bioactive peptides. As expected, preadministration of a carboxypeptidase inhibitor enhanced the systemic shock induced by the intestinal ischaemia. However, when the complement level was suppressed by CVF treatment, no fatal systemic shock was induced by the intestinal ischaemia even with preadministration of the carboxypeptidase inhibitor. These results indicate that complement plays a crucial role in systemic shock induced by intestinal ischaemia, and that anaphylatoxins generated by the complement activation should be involved in induction of the shock syndrome.

Role of gap junctions in inhibiting ischemia-reperfusion injury of rat gastric mucosa

Gap junctional intercellular communication (GJIC) is known to be important in the maintenance of tissue homeostasis. However, the role of GJIC in gastric mucosa has not been well investigated. We tested the hypothesis that maintenance of GJIC protects rat gastric mucosa against ischemia-reperfusion (I/R) stress by using irsogladine, an activator of GJIC, and octanol, an inhibitor of GJIC. Intragastric perfusion with octanol before ischemia resulted in a significant increase in 51Cr-EDTA clearance after reperfusion. Intraduodenal pretreatment with irsogladine attenuated the increase in 51Cr-EDTA clearance produced by octanol in a dose-dependent manner. Epithelial gap junctions reacted with anticonnexin-32 monoclonal antibodies were not changed after I/R stress alone. Intragastric perfusion with octanol caused a significant reduction in immunoreactive connexin-32 spots, which was completely reversed by irsogladine. These results indicate that inhibition of GJIC weakens the barrier function of gastric mucosa and subsequently causes damage of the barrier function in combination with I/R. Facilitation of GJIC and maintenance of gap junctions protect gastric mucosal barrier functions by potentiating cellular integrity.

Intrahepatic biliary papilloma morphologically similar to biliary cystadenoma

Abstract  A 37‐year‐old man presented complaining of epigastralgia. Abdominal ultrasonography revealed the presence of a papillary tumor (9 mm in diameter) in the cystic lesion (18 mm in diameter) in hepatic segment 4, which was accompanied by mild intrahepatic bile duct dilatation. Although abdominal computed tomography also showed the cystic lesion, it did not show papillary tumors inside the lesion. Endoscopic retrograde cholangiography showed the communication between the cystic lesion and the left hepatic duct. In addition, mucus was observed in the common bile duct. When transpapillary intraductal ultrasonography was performed through the left hepatic duct using a fine ultrasonic probe, a hyperechoic papillary and lobulated tumor was clearly shown in the cystic lesion. The wall of the cyst was smooth and there was no sign of tumor infiltration. Based on these findings, biliary cystadenoma was diagnosed and an extended left lobectomy was carried out. However, pathological findings postoperatively revealed that the lesion was a localized biliary papilloma, developing and extending to the intrahepatic duct. This case is rare and there have been no published reports describing a biliary papilloma morphologically similar to biliary cystadenoma.

SOLITARY RECTAL ULCER SYNDROME ACCOMPANIED BY SUBMUCOSAL INVASIVE CARCINOMA

We report a case of carcinoma in solitary rectal ulcer syndrome. The diagnosis was made by colonoscopic appearance and biopsy. A tumor measuring 0.9 × 0.6 cm was found in a resected solitary rectal ulcer. The lesion exhibited typical histological features of solitary rectal ulcer syndrome, with a well differentiated adenocarcinoma invading submucosal layers and some dysplastic glands. We believe that the adenocarcinoma represents a malignant transformation from solitary rectal ulcer syndrome, because similar to longstanding chronic idiopathic colitis, colorectal dysplasia and carcinoma may develop.

Exophytic pedunculated gastrointestinal stromal tumor with remarkable cystic change

A 59-year-old man with bloody stools, and previously diagnosed with sigmoid colon carcinoma, visited our hospital. Preoperative abdominal ultrasonography (US) showed another tumor, with an uneven irregular surface, measuring about 9 × 5 cm, below the left hypochondrium. The tumor consisted of several cysts. Abdominal computed tomography (CT) showed a multicystic tumor attached to the stomach, and its septum and marginal region were intensely stained on contrast imaging. On magnetic resonance imaging (MRI), low and markedly high signals were revealed in the tumor on T1-weighted and T2-weighted sequences, respectively. Contrast imaging of the upper digestive tract showed extramural compression of the greater curvature of the antral stomach by the tumor. The tumor was partially imaged by endoscopic ultrasonography (EUS), but continuity to the stomach was not confirmed. On abdominal angiography, the tumor was slightly stained via the gastroepiploic arteries. Surgical treatment was performed to excise both the gastric tumor and the sigmoid colon carcinoma. The gastric tumor was removed with gastric wall tissue where the tumor was attached to a 2-cm pedicle. It was multicystic, contained watery fluid, and had a smooth outer surface. Histologically, the tumor consisted of multiple irregular cysts without epithelial lining, and solid epitheloid cell nests in between. The tumor cells had clear or eosinophilic cytoplasm and round nuclei. No mitotic figures were seen. The tumor cells in the pedicle were connected with the muscularis propriae of the stomach. Immunohistochemistry showed c-kit-positive, CD34-positive smooth muscle actin (SMA)-negative, and S-100-negative staining of tumor cells. The final diagnosis was gastrointestinal stromal tumor (GIST).

Effect of epidermal growth factor in combination with sucralfate or omeprazole on the healing of chronic gastric ulcers in the rat

Epidermal growth factor (EGF) has been shown to enhance healing of experimental gastric ulcers when given subcutaneously or orally in the drinking water. This effect of EGF occurs without reducing gastric acid secretion. On the other hand, EGF reportedly is excreted rapidly from gastric lumen when administered by intragastric bolus. This suggests that further stimulation of ulcer healing may be expected if EGF is given with an acid-suppressive agent or with an agent allowing EGF to remain in rat gastric lumen at high concentrations. In the present study, EGF administered by gastric intubation at a dose of 10 μg/kg, which is three times smaller than reported in previous studies, was evaluated for its effect on acetic acid-induced rat gastric ulcers in combination with sucralfate or omeprazole. Sucralfate is well known selectively to bind proteins covering the ulcer base, and omeprazole is a potent acid-suppressive agent. Prior to the study of combined EGF and sucralfate oral sucralfate was continued to allow endogenous gastric EGF and mouse EGF given exogenously to remain at high concentrations in gastric contents and tissues. EGF and sucralfate (2 g/kg/day) given alone failed to stimulate ulcer healing in submandibularectomized rats (SMR rat) whose endogenous gastric EGF was depleted. However, the combination of both drugs administered at the same doses significantly accelerated ulcer healing in the SMR rat. Omeprazole (200 mg/kg/day) significantly enhanced ulcer healing regardless of removal of the submandibular glands. The combination of EGF and omeprazole further stimulated ulcer healing in the SMR rat. These results suggest that a small dose of EGF administered by gastric intubation may accelerate healing of chronic gastric ulcers when given in combination with a protein-binding agent (sucralfate) or a potent gastric acid-suppressive agent (omeprazole).