A mechanism for abnormal angiogenesis in human radiation proctitis: analysis of expression profile for angiogenic factors.

BACKGROUND: Radiation proctitis is an increasingly prevalent problem, with many patients being treated with radiotherapy for pelvic cancers. However, the mechanisms by which radiation proctitis develops in humans are not well understood. In this study, the expression profiles of angiogenic factors were analyzed to clarify their role in the etiology of radiation proctitis. METHODS: Rectal biopsies were taken from 8 patients with radiation proctitis and 8 normal subjects. Protein lysates of the tissues were applied to an antibody array for angiogenesis-related factors. The mRNA level of each factor was evaluated by Taqman real-time PCR. Immunohistochemistry was performed using the labeled streptavidin biotin method. RESULTS: Antibody array analysis revealed 2.12- to 7.31-fold higher expression levels of angiogenin, fibroblast growth factor 1 (FGF1), endoglin, matrix metalloproteinase (MMP)-8, urokinase-type plasminogen activator (uPA) and maspin in radiation proctitis tissues compared with normal rectal mucosa. The mRNA level of each factor in radiation proctitis tissue was significantly higher than in normal rectal mucosa, suggesting their transcriptional activation. Immunohistochemical staining showed strong expression of angiogenin and maspin in rectal epithelia, MMP-8 and uPA in infiltrating lymphocytes, FGF1 in fibroblasts and endoglin in endothelial cells. The expression of VEGF was not evident. CONCLUSIONS: Our results suggest that in radiation proctitis, MMP-8 and uPA cooperatively degrade the extracellular matrix and basement membrane to provide space for angiogenesis. Simultaneously, angiogenin and FGF1 promote endothelial cell proliferation, and endoglin induces vessel formation, culminating in angiogenesis. Inhibitors of angiogenic factors such as angiogenin and FGF1 may be effective for treating radiation proctitis.

[Successful rituximab monotherapy in a patient with mucosa-associated lymphoid tissue lymphoma of the rectum with trisomy 3, 18].

A 62-year-old man was referred to our hospital with enlargement of mucosa-associated lymphoid tissue (MALT) lymphoma of the rectum after the eradication of Helicobacter pylori. The patient was given a diagnosis of stage I MALT. Endoscopic observation revealed an enlarged rectal tumor with 3, 18 double trisomy. Rituximab monotherapy was given and complete remission was achieved. Rituximab monotherapy can be useful for MALT lymphoma of the rectum.

Migrated endoclip and stone formation after cholecystectomy: a case treated by endoscopic sphincterotomy.

Endoclip migration into the common bile duct following laparoscopic cholecystectomy (LC) is an extremely rare complication. Migrated endoclip into the common bile duct can cause obstruction, serve as a nidus for stone formation, and cause cholangitis. We report a case of cholangitis due to a migrated endoclip and consequent choledocholithiasis 6 years after LC, which was successfully treated by endoscopic extraction.

[Cancer chemoprevention-basic and clinical aspects].

Cancer chemoprevention is the use of agents to inhibit, delay or reverse carcinogenesis, and was proposed in the United States in view of the cost-benefits. Since recent progress in molecular biology revealed several signal transduction routes in carcinogenesis, the search for mechanism-based chemopreventive agents is under way. Many chemopreventive clinical trials for various cancers including colorectal cancer, prostate cancer and breast cancer, have been performed. Chemoprevention to eradicate viruses or bacteria such as hepatitis viruses or Helicobacter pylori is also important in order to prevent development of cancer.

Infrared fluorescence endoscopy for the diagnosis of superficial gastric tumors.

BACKGROUND: Indocyanine green (ICG) is a fluorescent marker that is excited by rays at a wavelength of 768 nm to emit fluorescence at a wavelength of 807 nm in the infrared (IR) range. We developed an IR fluorescence endoscope (IRFE) to observe superficial gastric tumors and assessed its clinical usefulness. OBJECTIVE: To evaluate the clinical usefulness of an IRFE for the assessment of superficial gastric tumors. DESIGN: An observational study. SETTING: University hospital. INTERVENTIONS: Newly developed IRFE. PATIENTS: Thirty patients with gastric tumors were enrolled in this study, and their lesions were subjected to endoscopic submucosal dissection (ESD), or laparoscopic gastrectomy after observation with the IRFE. METHODS: Gastric lesions were subjected to conventional observation, followed by IR fluorescence observation before and after intravenous ICG (0.01 mg/kg) injection. MAIN OUTCOME MEASUREMENTS: The relationship between the positive fluorescence and invasivity of each tumor. RESULTS: Fluorescence was positive in 8 of 10 gastric cancers with submucosal invasion (80%) and 1 of 20 adenomas or intramucosal gastric cancers (5%); the difference was statistically significant (P<.01). CONCLUSION: IRFE is a useful diagnostic tool for estimating the invasivity of gastric tumors.

[A case of parathyroid hormone-related peptide producing gallbladder carcinoma presenting humoral hypercalcemia of malignancy].

Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive.

Relationships between insulin resistance, blood glucose levels and gastric motility: an electrogastrography and external ultrasonography study.

BACKGROUND: Detailed information concerning the influence of insulin resistance on gastrointestinal motility are not available. METHODS: The relationship between insulin resistance and gastric motility and emptying, and changes in gastric motility with changes in blood glucose level were investigated using electrogastrography (EGG) and external ultrasonography in 20 non-diabetic subjects. The homeostasis model assessment ratio (HOMA-R) was used as an index of insulin resistance. The cut off value for HOMA-R was set at 1.7. Subjects with HOMA-R > or = 1.7 were the high HOMA-R group, and HOMA-R < 1.7 were the normal HOMA-R group. In the EGG data, a Fast Fourier Transform (FFT) analysis was performed, and the mean peak power was compared among brady-, normal-, and tachy-gastria. RESULTS: In the fasting state, the ratios of brady-gastria in EGG and HOMA-R were significantly positively correlated, and the ratios of normal-gastria and HOMA-R were significantly negatively correlated. When glucose was intravenously administered, the ratio of normal-gastria was significantly decreased and the ratio of brady-gastria was significantly increased in subjects with a high HOMA-R. In a gastric emptying test by external ultrasonography, gastric emptying activity was significantly decreased in subjects with a high HOMA-R. CONCLUSIONS: We conclude that insulin resistance induces abnormal gastric motility. Though abnormal gastric motility is related to HOMA-R, the findings herein suggest that incretin, showing insulin resistance, or an adipocyokine might be related to the differences in EGG in both groups. The relation between abnormal gastric motility and other serum parameters (incretin, adipocyokine, etc) would contribute to a better understanding of this process.

The use of electrogastrography and external ultrasonography to evaluate gastric motility in Crohn's disease.

Although Crohn's disease is associated with various digestive symptoms, there have been few reports on gastric motility. In this study, we conducted a study of gastric motility in Crohn's disease using 20 healthy subjects (N group) and 15 patients with Crohn's disease (C group) by electrogastrography (EGG) using a Nipro electrogastrograph. An EGG was recorded for 30 minutes in a fasting state and after ingestion of 300 ml of a liquid meal. As an index of gastric emptying, the rate of change in the cross-sectional area of the gastric antrum was measured 1 and 15 minutes after ingestion of the liquid meal by external ultrasonography. In an EGG frequency analysis, waveforms with a peak of 3 cycles/minute (cpm) were noted in the N group, and the peak amplitude increased significantly after the ingestion of food. In the C group, division of the normal-gastria component was noted after the ingestion of food in 5 patients (33.3%). In a comparison of the peak amplitudes of fasting brady-gastria, normal-gastria, and tachy-gastria between the N and C groups, the peak amplitude was significantly increased in normal-gastria in the N group, and in brady-gastria and tachy-gastria in the C group. In a comparison of the rates of food ingestion-induced changes in the peak amplitudes for brady-gastria, normal-gastria, and tachy-gastria between the N and C groups, the peak amplitudes were significantly increased in normal-gastria in the N group, but not in the C group. In the case of gastric emptying investigated by external ultrasonography, the rate of food ingestion-induced change in the cross-sectional antrum area was significantly lower in the C group (50.5+/-9.2%) than in the N group (65.0+/-8.5%). For gastrointestinal motility, a 3 cpm normal-gastria represents efficient gastric motility. In the C group, the peak amplitudes of brady-gastria and tachy-gastria were significantly increased, but were low in normal-gastria in the fasting EGG, postprandial division of the normal-gastria component was noted, and the rate of food ingestion-induced increase in the normal-gastria peak amplitude was significantly lower than that in the N group, suggesting that patients with Crohn's disease have a functional abnormality in, not only the small and large intestine, but also the stomach.

Principle and clinical usefulness of the infrared fluorescence endoscopy.

Since there is no infrared fluorescence materials in the living body, infrared fluorescence labeling materials are very useful for making a diagnosis of a micro cancer. We have developed an infrared fluorescence endoscope (IRFE) and indocyanin green (ICG)-derivative as infrared fluorescence labeling materials to evaluate gastrointestinal neoplastic lesions. The study aims were to apply an IRFE and to demonstrate its usefulness in detecting cancerous tissue using an antibody coupled with ICG-derivative. IRFE consisted of an infrared endoscope equipped with excitation (710-790 nm) and barrier (810-920 nm) filters and an intensified CCD camera. We have developed ICG N-hydroxy sulfo succinimide ester (ICG-sulfo-OSu) and 3-ICG-acyl-1, 3-thiazolidine-2-thione (ICG-ATT) as an infrared fluorescent-labeling reagent. ICG-derivative-labeled mouse anti-human carcinoembryonic antigen (CEA) antibody and MUC1 antibody were employed in this study. Moreover, we examined the ability of a reinforcement agent, octylglucoside, to intensity fluorescence from the labeled antibody. Biopsy specimens of gastric cancer were stained with anti-CEA antibody by the avidin-biotinylated peroxidase complex method. Among the positive specimens, freshly resected stomach from three cases were used for the infrared (IR) imaging analysis. The incubation of freshly resected stomach specimens with ICG-anti-CEA antibody-complex resulted in positive staining of the tumor sites by IRFE, and the IR fluorescent images correlated well with the tumor sites. The immunohistochemical studies suggested that the intensity of IR fluorescence of ICG-ATT-MUC1 was stronger than that of ICG-sulfo-OSu. In tumor sections, the reinforcement agent intensified fluorescence, ever at low antibody concentrations. Therefore, we conclude that an anti-CEA (and/or MUC1) antibody with affinity for cancerous lesions and labeled with ICG-derivative can be imaged with this IRFE. Specific antibodies tagged with ICG-derivative with the reinforcement agent can label cancer cells and generate a strong enough fluorescent signal to detect small cancers when examined with an IR fluorescence endoscope.